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Ameliorative effects of Stinging Nettle (Urtica dioica) on testosterone induced prostatic hyperplasia in rats
Andrologia
Abstract
The present study investigated the effects of stinging nettle (Urtica dioica L.) (UD) on benign prostatic hyperplasia (BPH) induced by testosterone. In vitro studies were conducted to assess the 5α-reductase inhibitory potential of UD. Two biochemical markers viz., β-sitosterol and scopoletin, were isolated and characterised in the extracts utilising High-performance thin layer chromatographic, FTIR, NMR and overlain UV spectral studies. Hyperplasia was induced in rats by subcutaneous administration of testosterone (3 mg kg(-1) s.c.) for 28 days in all the groups except the vehicle-treated group. Simultaneous administration of petroleum ether and ethanolic extracts (10, 20 and 50 mg kg(-1) p.o.) and isolated β-sitosterol (10 and 20 mg kg(-1) p.o.) was undertaken. Finasteride was used as a positive control (1 mg kg(-1) p.o.). Measurement of prostate/body weight ratio, weekly urine output and serum testosterone levels, prostate-specific antigen levels (on day 28) and histological examinations carried out on prostates from each group led us to conclude that UD can be used as an effective drug for the management of BPH.
... Ud is a rich source of iron, ascorbic acid, carotenoids, essential amino acids and fatty acids [4]. A more recent and also the most reported use of Ud is the treatment of symptomatic benign prostatic hyperplasia (BPH) [1][2][3][4][5][6]. In addition to its effects on relevant hormones and cytokines, its 5-alpha-reductase (5α-R) inhibition activity has also role in its therapeutic merit [1,2,4,5,7,8]. ...
... A more recent and also the most reported use of Ud is the treatment of symptomatic benign prostatic hyperplasia (BPH) [1][2][3][4][5][6]. In addition to its effects on relevant hormones and cytokines, its 5-alpha-reductase (5α-R) inhibition activity has also role in its therapeutic merit [1,2,4,5,7,8]. Inhibition of 5α-R obviates the conversion of testosterone to dihydrotestosterone (DHT), whose high levels are linked with BPH and androgenetic alopecia (AGA) [9][10][11]. ...
... It was previously reported the inhibition of 5α-R by Ud extracts, but until now this was only shown in prostatic tissues, using biochemical enzyme inhibition methods [5,7,8]. Although it was reported the suppression of 5α-RII gene expression on dermal papilla cells, this study was performed with a mixture of six different plants including Ud [13]. ...
Urtica dioica (Ud) is a perennial plant of temperate climate regions and has been reported therapeutic activity against benign prostate hyperplasia, mainly due to its 5-alpha-reductase (5α-R) inhibition feature, which has been singly shown only in prostatic tissues until now. Also considering its use in traditional medicine against some dermatological problems and hair loss, we performed an in-vitro study to reveal its 5α-R inhibition activity in skin cells whether this plant may have a therapeutic potential against androgenic skin diseases. After the preparation of Ud leaf extract and determination of non-cytotoxic concentration, cultured HaCaT cells were treated with the plant extract. RNA isolations were carried out from both non-treated and treated cell groups. cDNA synthesis was performed using gene specific primers of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as reference gene and 5α-R type II (5α-RII) as study material. Gene expressions were determined by real time reverse transcription quantitative polymerase chain reaction analysis. Results were represented as 'Target/GAPDH Fold Change'. Results of gene expression analysis showed that plant extract caused statistically significant downregulation of 5α-RII gene expression (p=0.0021) in treated cells, compared to untreated control cells, and ended up with 0.5873±0.0586 fold change. This study is the first one showing the suppression of 5α-RII gene expression on skin cells with unmixed or solitary Ud extract. With the currently reported anti-androgenic activity in HaCaT cells, it can be suggested that Ud has a solid scientific base and may have a promising future in cosmetic dermatology, and new product development against androgenic skin diseases.
... • Anti-inflammatory and anti-proliferative [15] • Inhibition of 5-alpha-reductase [16] • Inhibition of prostate growth [16] • ...
... • Anti-inflammatory and anti-proliferative [15] • Inhibition of 5-alpha-reductase [16] • Inhibition of prostate growth [16] • ...
... The mechanism of action of urtica dioica has been shown to involve 5-alpha-reductase inhibitory activity on testosterone [16]. Antiproliferative effects have also been demonstrated to affect just epithelial cells [15]. ...
Citation: Antoniou, V.; Gauhar, V.; Modi, S.; Somani, B.K. Role of Phytotherapy in the Management of BPH: A Summary of the Literature. Abstract: Benign prostatic hyperplasia (BPH) describes the non-malignant enlargement of the prostate. It is both common and growing in incidence. Treatment is multimodal, involving conservative, medical, and surgical interventions. This review aims to examine the evidence base for phytotherapies, specifically analyzing their role in treating lower urinary tract symptoms (LUTS) attributable to BPH. A literature search was completed, specifically looking for randomized control trials (RCTs) and systematic reviews involving phytotherapy treating BPH. Specific emphasis was placed on exploring substance origin, the proposed mechanism of action, evidence of efficacy, and the side-effect profile. Several phytotherapeutic agents were evaluated. These included serenoa repens, cucurbita pepo, and pygeum Africanum, among others. For most of the reviewed substances, only modest effectiveness was reported. Generally, though, all treatments were tolerated well with minimal side effects. None of the treatments discussed in this paper form part of the recommended treatment algorithm in either European or American guidelines. We, therefore, conclude that phytotherapies, in the treatment of LUTS attributable to BPH, do provide a convenient option for patients, with minimal side effects. At present, however, the evidence for the usage of phytotherapy in BPH is inconclusive, with some agents having more backing than others. This remains an expansive field of urology whereby there is still more research to be done.
... Compelling pre-clinical evidence revealed a hypoglycemic activity for the plant, and a meta-analysis carried out by Ziaie and collaborators (2019) corroborated the beneficial effects of U. dioica on glycemic levels. Pre-clinical in vitro and in vivo evidence also revealed the ability of U. dioica to inhibit 5-α-reductase activity, leading to an elevation of testosterone levels [34]. ...
... The phytoanabolic extracts were administered daily by oral route, for eight weeks, beginning eight weeks after castration. The doses of the extracts were based on a series of previous publications showing efficacy and low toxicity in different experimental paradigms [34,[45][46][47][48][49][50][51][52][53][54][55][56][57][58][59]. A scheme showing the timeline for the experimental protocols is provided in the Supplementary Figure S2. ...
... Indeed, its main application is related to treatment of benign prostatic hyperplasia. In addition, some studies have described benefits for U. dioica extract for management of diabetes complications [34,57,89]. More recently, it was demonstrated that supplementation with plain U. dioica led to body weight loss in mice that received a high-fat diet, via modulation of genes related to lipid and glucose metabolism [33]. ...
Dry extracts from the Eurasian plants, Ajuga turkestanica, Eurycoma longifolia, and Urtica dioica have been used as anabolic supplements, despite the limited scientific data on these effects. To assess their actions on early sarcopenia signs, male and female castrated mice were supplemented with lyophilized extracts of the three plants, isolated or in association (named TLU), and submitted to resistance exercise. Ovariectomy (OVX) led to body weight increase and non-high-density cholesterol (HDL) cholesterol elevation, which had been restored by exercise plus U. dioica extract, or by exercise and TLU, respectively. Orchiectomy (ORX) caused skeletal muscle weight loss, accompanied by increased adiposity, being the latter parameter reduced by exercise plus E. longifolia or U. dioica extracts. General physical activity was improved by exercise plus herbal extracts in either OVX or ORX animals. Exercise combined with TLU improved resistance to fatigue in OVX animals, though A. turkestanica enhanced the grip strength in ORX mice. E. longifolia or TLU also reduced the ladder climbing time in ORX mice. Resistance exercise plus herbal extracts partly altered gastrocnemius fiber size frequencies in OVX or ORX mice. We provide novel data that tested ergogenic extracts, when combined with resistance exercise, improved early sarcopenia alterations in castrated male and female mice.
... After centrifugation at 3000 rpm for 15 min at 4 • C, the collected supernatant was stored at − 20 • C for the determination of total protein in the prostate. The prostate wet weight was calculated as the prostate weight/body weight ratio as described by Nahata and Dixit (2012). The size of the prostate was measured using a 1 mm precision sliding caliper (IGAGING®) and prostate volumes were calculated using the formula of Rahul et al. (2014): volume = length × weight × height × π/6. ...
... These later would act via estrogen receptors in prostate and activate the proliferation of stromal and epithelial cell autocrine and paracrine pathways (Devlin, 2021). In this study, the testosterone administration induced a significant increase in the prostate relative weight, prostate volume and prostate epithelium height compared to normal rats, confirming the set up of BPH (Nahata and Dixit, 2012). In fact, prostate weight and prostate volume are crucial indicators for the diagnosis of BPH and for the screening of potential beneficial compounds. ...
... Benign prostate hyperplasia (BPH) was induced by subcutaneous injection with 25 mg/kg b.w of SustanonR '250' (Testosterone esters), manufactured by Pharmatec Pakistan LTD under license from N.V. Organon OSS, The Netherlands for 28 days in male rats to be used for this study with exception of Group 1 (Normal control) [10]. ...
... The 5αreductase is the enzyme that converts testosterone to dihydrotestosterone (DHT) which is implicated in development of BPH [1]. Several plants have been reported to have 5α-reductase inhibitory activity and hence prevent the development of BPH [31,10]. There is strong evidence that phytochemical agents are effective inhibitors of 5α-reductase that consequently leads to reduction in DHT concentrations and slows down BPH [32]. ...
Jathropha curcas roots extract have been claimed by traditionalist to have remedial effects on benign prostate hyperplasia (BPH). This study is aimed at evaluating the effects of methanol extract of Jathropha curcas roots on testosterone-induced benign prostate hyperplasia in male albino rats. A total of 15 male albino rats were divided into 5 groups of 3 each. The groups were a normal control, positive control, standard control (Dutasteride 0.5 mg/kg), and two test groups (50 and 100 mg/kg b.w) of the treatment extract. Benign prostate hyperplasia was induced using 25 mg/kg b.w of testosterone propionate subcutaneously for 28 days in all the groups with exception of the normal control group. This was followed by treatment with Jathropha curcas roots extracts at doses of 50 and 100 mg/kg b.w for 2 weeks daily by oral gavage. At the end of the treatment period, the animals were weighed, sacrificed and blood was collected by ocular puncture. Biochemical assays such as liver function test and antioxidant enzymes, MDA, prostate specific antigen (PSA), testosterone and zinc concentration levels were analyzed using standard procedures. Prostate weight (prostate /body weight ratio) was calculated and histological changes in the prostate were examined. The result showed non-significant (p > 0.05) difference in ALT, AST and ALP. There was also non-significant (p > 0.05) difference in MDA and SOD, however CAT significantly (p < 0.05) increased when group 5 was compared with group 2. Prostate specific antigen significant (p < 0.05) decreased when group 4 and 5 were compared with group 2.There was also a significant (p < 0.05) decrease in testosterone level, when group 5 was compared with group 2. Zinc concentration significantly (p < 0.05) increased when group 5 was compared with group 2. The relative prostate weight showed a significant (p < 0.05) decrease when group 5 was compared with group 2 in a dose dependent manner. Histological changes also observed in the ventral lobe of the BPH induced prostate was suppressed following treatment with the plant extract in a dose dependent manner. These results suggest that methanol extract of Jathropha curcas roots may be effectively used in the management of BPH. Keywords: Jathropha curcas roots, testosterone and benign prostate hyperplasia (BPH)
... Benign prostate hyperplasia (BPH) was induced by subcutaneous injection with 25 mg/kg b.w of SustanonR '250' (Testosterone esters), manufactured by Pharmatec Pakistan LTD under license from N.V. Organon OSS, The Netherlands for 28 days in male rats to be used for this study with exception of Group 1 (Normal control) [10]. ...
... The 5αreductase is the enzyme that converts testosterone to dihydrotestosterone (DHT) which is implicated in development of BPH [1]. Several plants have been reported to have 5α-reductase inhibitory activity and hence prevent the development of BPH [31,10]. There is strong evidence that phytochemical agents are effective inhibitors of 5α-reductase that consequently leads to reduction in DHT concentrations and slows down BPH [32]. ...
... Carbohydrates, sterols, flavonoids, triglycerides, fatty acids [110,111] • Inhibits 5α-reductase [111] • >Inhibits formation of DHT and some testosterone metabolites [111] • Inhibits the conversion of testosterone into DHT [111] • Inhibition of α -receptor binding [111] • Inhibits the receptor binding of androgens [111] • Anti-proliferative effect [111] • Inhibition of eicosanoid synthesis [111] • Spasmolytic effects [111] • Anti-inflammatory activity [111,112] Urtica dioica root Sterols, flavonoids, tannins, acids, minerals, lectins, polysaccharides ceramides, monoterpenoids, fatty triterpene, and phenylpropane [4,9,[113][114][115][116] • Anti-proliferative, anti-inflammatoryinhibition of COX and lipoxygenase [4] • Inhibits TNF activity [4] • Stimulates activity of T-lymphocytes and the complement activation [117] • Inhibits the connecting of sex hormone binding globulin [118] • Inhibits prostate growth [119,120] ...
... Simultaneous administration of petroleum ether and ethanolic extracts (10, 20 and 50 mg/kg −1 per os) and isolated β-sitosterol (10 and 20 mg/kg −1 per os) was undertaken. Measurement of prostate/body weight ratio, weekly urine output and serum testosterone levels, PSA levels (on day 28), and histological examinations carried out on prostates from each group allowed the conclusion that U. dioica can be used as an effective drug for the management of BPH [120]. ...
Benign prostatic hyperplasia (BPH) is one of the most common urinary diseases affecting men, generally after the age of 50. The prevalence of this multifactorial disease increases with age. With aging, the plasma level of testosterone decreases, as well as the testosterone/estrogen ratio, resulting in increased estrogen activity, which may facilitate the hyperplasia of the prostate cells. Another theory focuses on dihydrotestosterone (DHT) and the activity of the enzyme 5α-reductase, which converts testosterone to DHT. In older men, the activity of this enzyme increases, leading to a decreased testosterone/DHT ratio. DHT may promote prostate cell growth, resulting in hyperplasia. Some medicinal plants and their compounds act by modulating this enzyme, and have the above-mentioned targets. This review focuses on herbal drugs that are most widely used in the treatment of BPH, including pumpkin seed, willow herb, tomato, maritime pine bark, Pygeum africanum bark, rye pollen, saw palmetto fruit, and nettle root, highlighting the latest results of preclinical and clinical studies, as well as safety issues. In addition, the pharmaceutical care and other therapeutic options of BPH, including pharmacotherapy and surgical options, are discussed, summarizing and comparing the advantages and disadvantages of each therapy.
... Benign prostate hyperplasia (BPH) was induced by subcutaneous injection with 25 mg/kg b.w of SustanonR '250' (Testosterone esters), manufactured by Pharmatec Pakistan LTD under license from N.V. Organon OSS, The Netherlands for 28 days in male rats to be used for this study with exception of Group 1 (Normal control) [10]. ...
... The 5αreductase is the enzyme that converts testosterone to dihydrotestosterone (DHT) which is implicated in development of BPH [1]. Several plants have been reported to have 5α-reductase inhibitory activity and hence prevent the development of BPH [31,10]. There is strong evidence that phytochemical agents are effective inhibitors of 5α-reductase that consequently leads to reduction in DHT concentrations and slows down BPH [32]. ...
... Nettle root extract has at least 18 types of sterols and 8 types of lignan [22]. Nettle prevents formation of the active form of testosterone, dihydrotestosterone by inhibition the enzyme 5-alpha reductase [23,24]. In the study of Nahata and Dixit, effect of nettle extract was investigated followed by prescription of testosterone for 28 days in a subcutaneous form and with dose of 3 mg/Kg of rat's body weight that was similar to the present study [24]. ...
... Nettle prevents formation of the active form of testosterone, dihydrotestosterone by inhibition the enzyme 5-alpha reductase [23,24]. In the study of Nahata and Dixit, effect of nettle extract was investigated followed by prescription of testosterone for 28 days in a subcutaneous form and with dose of 3 mg/Kg of rat's body weight that was similar to the present study [24]. Nettle root extract inhibits aromatase and thus prevents the conversion of testosterone to estrogen, and also prevents androgen binding to androgen receptors [6]. ...
Background: Hyperactivity of testosterone is one cause of infertility and its incorrect use can produces reproductive disorders. Nettle (Urtica dioica) has antiandrogenic effect and may antagonized effect of testosterone. In present study structure of testes of golden hamster was evaluated after testosterone and extract. Materials and Methods: In this experimental and animal modeling study, twenty male mature hamsters were divided to 4 groups, group 1 was control, group 2 received testosterone at dose 3 mg/kg subcutaneously, group 3 received nettle extract dose 30 mg/kg orally and group 4 received testosterone and nettle for 30 days daily. The hamsters were euthanized and testes were removed and detected macroscopic parameters (weight, height, wide and volume) and fixed with formalin. The samples were sectioned and colored with H & E. Results: The volume, weight, length and wide of testes was at least in testosterone group and statistically was lesser than control and testosterone-nettle group (p<0.05), but did not the height epithelium of seminifer tubules, compact of spermatogenic cells and number of serotolli cells in testosterone group was lesser than control group significantly (p<0.05). Conclusion: The nettle extract decreased histological changes of testes by testosterone and improved its structure.
... Among the plants used in our formulation Urtica dioica (Ud) is the most widely studied one. Symptomatic benign prostate hyperplasia (BPH) is the best researched indication of this plant which is mainly due to its 5α-R inhibition activity (23,24,25). Inhibition of 5α-R precludes the conversion of testosterone to dihydrotestosterone (DHT) high levels of which are associated with BPH (26). ...
... which is mainly due to its 5α-R inhibition activity (23,24,25). Inhibition of 5α-R precludes the conversion of testosteron to dihydrotestosteron (DHT) high levels of which are associated with In a study performed with Equisetum arvense (Ea) alone and with combination of some other plants, Ea suppressed the superoxide anion levels in the xanthine/ xanthine oxidase system and abolished the hydroxil radical. ...
Background: Currently while, topical minoxidil and oral finasteride are the only medications approved in androgenetic alopecia (AGA), the cause oriented treatment and immunsupres-sive treatment are being performed in telogen effluvium (TE) and alopecia areata (AA) respectively. Considering the inflammatory factors in the pathogenesis of these three nonscarring al-opecia forms, we have formulated a mixture for topical usage composed of six different herbal extracts (HE) which have already known antiinflammatory and antioxidant features. Materials and Methods: In addition to performing the phytochemical analysis of HE, we detected the gene expression level of IL-1α, the crucial hair loss mediator, for the putative efficacy in non-scarring alopecia. Cell proliferation assay was performed by XTT reagent. After determination of non-cytotoxic concentration, HaCaT cells were treated with HE. RNA isolations were carried out from both non-treated and treated cell groups by using TRI-reagent. Gene expressions of IL-1α and as control GAPDH were determined by RT-qPCR analysis. Results: Results were represented as "IL-1α/GAPDH Fold Change". HE solution caused statistically significant downregulation of IL-1α gene expressions (p<0.0001), compared to untreated control cells. HE treatment ended up with 0.1900 fold change for IL-1α. Conclusion: IL-1α is a direct growth inhibitory agent in hair follicles and an important actor in the pathogenesis of AGA , TE, and AA. Considering together the vitamins, flavonoids, and trace elements identified in the phy-tochemical analyses and downregulation of IL-1α in HaCaT cells, our HE may be an auxiliary agent in the therapy of these three nonscarring alopecia forms.
... Consistent with our results, Bakam, et al. [14] reported that testosterone injection resulted in a considerable increase in prostate relative weight, prostate volume, and prostate epithelium height compared to normal rats, hence validating the establishment of BPH [15]. Prostate weight and volume are essential metrics for diagnosing (BPH) and for evaluating possibly advantageous substances. ...
Background: The oil from the pumpkin (Cucurbita pepo) seed is claimed to be useful in the management of benign prostatic hyperplasia. This investigation seeks to examine the effect of pumpkin seed oil on testosterone-induced hyperplasia of the prostate in a dog model. Materials and methods: A total of 6 sexually mature male stray dogs (age: 2-4 years old; weight: 20-25 kg) were housed at the Animal Reproduction Research Institute. Animals were subdivided into 2 equal groups; Control group: continued to receive the same diet without treatment until the end of the study, BPH group: received Testosterone (75mg/dog) (Testonon®250: 0.3 ml/dog) and Estradiol Benzoate (0.75mg/dog) (Folon®: 0.2 ml /dog) via intramuscular injection on days 0, 21, 42, and 63 of the induction periods. The testosterone doses were doubled on days 21, 42, and 63. The same animals (n=3) were taken as Pumpkin treated group: this was a PBH group treated with the Pumpkin seed extract at the dose of 600 mg pumpkin seed oil for 30 days. Blood sampling was performed from the cephalic vein into plain glass tubes on days 0, and 63 before the injection of hormones during induction and after treatment. Results: Length, depth, height, and volume were significantly higher in the BPH disease group compared to the control group. Moreover, all these physical characteristics were decreased significantly in the Pumpkin treated group. PSA showed a statistically significant increase in the BPH-diseased group (.055±.005 mg/ml) compared to the control group and decreased significantly in the pumpkin-treated group (.024±.001 mg/ml) with no significant change in the testosterone level. Conclusion: The present study demonstrates that pumpkin seed oil extract effectively mitigates the growth and hyperplasia associated with benign prostatic hyperplasia as evidenced by substantial reductions in prostate length, depth, height, and volume, along with decreased PSA levels.
... Therefore, there has been a lot of interest lately in the usage of natural products and food supplements that have anticancer characteristics [49]. Different groups have determined the cytotoxic and antitumor properties of various species of the genus Urtica [50][51][52]. ...
Urtica dioica L. has been used as a natural remedy due to its healing properties for over 2000 years. The aim of this study is to investigate the chemical composition, antimicrobial, antioxidant, and antitumor properties in vitro of the aqueous extract of Urtica dioica leaves (AEUD). The chemical composition was assessed by an ultra-high-performance liquid chromatography system coupled to a benchtop QExactive high-resolution accurate mass spectrometry operating in a data-dependent acquisition mode as a non-target approach. Minimal inhibitory concentration (MIC) and disc diffusion were used to assess the antibacterial efficacy against nine bacterial strains. The antioxidant impact was assessed using DPPH, ABTS, FRAP, and ferrous ion-chelating ability assays. By using the MTT method, the cytotoxicity effect of AEUD on colon cancer cell HCT-116 was evaluated. Flow cytometry was used to analyze the cell cycle. Finally, the anti-migration and anti-invasion properties of AEUD on HCT-116 cells were estimated using the wound healing test and Transwell assays. AEUD is a rich source of phenolic compounds. The results of disc diffusion and MIC showed that the AEUD is more active against Gram-positive bacteria than against Gram-negative bacteria. MTT assay confirmed that the AEUD inhibited HCT-116 colon cancer cell proliferation. Findings of flow cytometry confirmed that cell cycle arrest occurred at the G2 phase. Additionally, AEUD had anti-migration and anti-invasion effects. This study shows that Urtica dioica aqueous leaf extract exhibits potential antibacterial, antioxidant, and antitumoral activities on HCT-116 colon cancer cells.
... PSA levels were evaluated to determine the degree of hyperplasia caused by testosterone injection in the prostate. For this purpose, serum PSA levels were quantified using a commercially available Elisa kit, following a previously described protocol [37]. The PSA Elisa kit (c.n.: E-EL-M0961, Elabscience) is designed for the quantitative measurement of total PSA levels. ...
Background/objectives:
Benign prostatic hyperplasia (BPH) is one of the most common chronic diseases affecting the urinary tract that occurs mainly in men over 40 years of age. Among the natural therapies, proanthocyanidins (PACs), which can treat a wide range of immune-mediated inflammatory diseases (IMIDs), have been shown to play an important role in the treatment of pathologies concerning prostate health. In this regard, the present study aimed to evaluate the different bioactivities of a grape seed extract (GSE), rich in polymeric PACs, and its version processed under alkaline conditions (ATGSE), characterized by a higher content of oligomeric PACs, in an animal model of BPH induced by subcutaneous injection of testosterone (1 mg/mouse).
Methods:
These latter were divided into a control group (vehicle, olive oil), a BPH group (testosterone 1 mg/mouse), and four treatment groups treated with GSE (500 mg/kg) and ATGSE (125, 250, 500 mg/kg) by oral gavage. At the experimental endpoint (4 weeks), hematological and biochemical analyses of blood and tissues were performed.
Results:
Data showed that oral administration of ATGSE (250 mg/kg) was significantly more effective than GSE in reducing prostate (p ≤ 0.0001) and seminal vesicle (p ≤ 0.0001) weight. Moreover, ATGSE exhibited enhanced effectiveness in significantly reducing PSA levels (p ≤ 0.0001 vs. GSE) and the expression of key pro-inflammatory cyto-chemokines in prostate and seminal vesicles homogenates.
Conclusions:
These findings pave the way for the clinical application of ATGSE as a nutraceutical and/or functional food.
... (Lemos et al., 2020), Solanum lyratum Thunb. (Kang et al., 1998), and Cirsium setidens (Dunn) Nakai (Ahn et al., 2014); in the roots of Hibiscus syriacus L. (Yun et al., 2001), Urtica dioica L. (Nahata and Dixit, 2012), Biebersteinia multifida DC. (Monsef-Esfahani et al., 2013), Gelsemium sempervirens L. (Khuda-Bukhsh et al., 2010), Saposhnikovia divaricata Turcz. Schischk (Kamino et al., 2016), Hypochaeris radicata L. (Jamuna et al., 2015), Argyreia speciosa L.f. (Kashyap et al., 2020), and Angelica pubescens Maxim. ...
Scopoletin is a coumarin synthesized by diverse medicinal and edible plants, which plays a vital role as a therapeutic and chemopreventive agent in the treatment of a variety of diseases. In this review, an overview of the pharmacology, pharmacokinetics, and toxicity of scopoletin is provided. In addition, the prospects and outlook for future studies are appraised. Scopoletin is indicated to have antimicrobial, anticancer, anti-inflammation, anti-angiogenesis, anti-oxidation, antidiabetic, antihypertensive, hepatoprotective, and neuroprotective properties and immunomodulatory effects in both in vitro and in vivo experimental trials. In addition, it is an inhibitor of various enzymes, including choline acetyltransferase, acetylcholinesterase, and monoamine oxidase. Pharmacokinetic studies have demonstrated the low bioavailability, rapid absorption, and extensive metabolism of scopoletin. These properties may be associated with its poor solubility in aqueous media. In addition, toxicity research indicates the non-toxicity of scopoletin to most cell types tested to date, suggesting that scopoletin will neither induce treatment-associated mortality nor abnormal performance with the test dose. Considering its favorable pharmacological activities, scopoletin has the potential to act as a drug candidate in the treatment of cancer, liver disease, diabetes, neurodegenerative disease, and mental disorders. In view of its merits and limitations, scopoletin is a suitable lead compound for the development of new, efficient, and low-toxicity derivatives. Additional studies are needed to explore its molecular mechanisms and targets, verify its toxicity, and promote its oral bioavailability.
... In light of such investigations, we conducted this study to examine if the chosen extracts can be used as hair loss prevention agents based on their cosmetological properties [30][31][32][33][34][35][36][37][38][39][40][41][42][43][44]. To achieve our goals, we evaluated the growth-proliferation abilities of these extracts using changes in the viability of human follicle dermal papilla cells. ...
Although hair loss plays a vital physiological function in present society, their impact on shaping self-esteem is undeniable. Even though there are numerous synthetic drugs available, these days, there are issues with safety, efficiency, and unclear time settings for required outcomes with the current synthetic drug remedies available; therefore, there is growing attention to discovering alternative methods to fight hair loss, primarily through plant-derived formulations. While earlier reports mostly focused on screening compounds or plant extracts affecting 5α-reductase, our research takes a unique direction. We employed a biochemical and molecular biological approach by delving into the complicated biosynthetic pathways involving 17β-hydroxysteroid dehydrogenase (17β-HSD) and 3β-hydroxysteroid dehydrogenase (3β-HSD) in producing testosterone derived from cholesterol. This process conceded requiring experimental results, posing insights into the control of the testosterone/dihydrotestosterone (DHT) production pathway. Our study confirms a discovery platform for finding potential candidates as hair loss inhibitors, highlighting exploring various biochemical mechanisms involving 17β-HSD and 3β-HSD in combination with medicinal plant extracts.
... Some of the latest studies have been published with sterol data from nettle seed oil ( Jafari et al., 2020 ;Petkova et al., 2020 ). Different studies on nettle root extracts used a variety of solvents like combination of cyclohexane, ethyl-acetate, 1-butanol, methanol and water ( Lichius & Muth, 1997 ), petroleum ether ( Nahata & Dixit, 2012 ), diethyl ether ( Sajfrtová et al., 2005 ), methanol ( Chaurasia & Wichtl, 1987 ;Gansser & Spiteller, 1995 ), aqueous solutions of ethanol or methanol ( Antonopoulou et al., 1996 ;Hartmann et al., 1996 ;Lichius & Muth, 1997 ), supercritical CO 2 ( K Ő szegi et al., 2015 ;Sajfrtová et al., 2005 ) and corn/sunflower oil ( Fedorovska et al., 2021 ). Six studies were focused on sterols ( Antonopoulou et al., 1996 ;Chaurasia & Wichtl, 1987 ;Fedorovska et al., 2021 ;Hartmann et al., 1996 ;Lichius & Muth, 1997 ;Sajfrtová et al., 2005 ), however only Chaurasia and Wichtl ( Chaurasia & Wichtl, 1987 ) detected eight and Fedorovska et al. (2021) five sterols. ...
... The administration of petroleum ether, ethanolic extracts 10, 20 and 50 mg/kgand isolated βsitosterol 10 and 20 mg/kg has been under taken for BPH studies. There was decrease in prostate/body weight ratio weekly urine out-put and serum testosterone levels, Prostate-specific antigen levels carried out which conclude that Urticadioica can be used for the management of BPH (Nahata and Dixit, 2012) [19] . ...
... Urtica dioica. Is the most widely studied ones symptomatic benign prostate hyperplasia (BPH) is the best researched indication of this plant which is mainly due to its 5α-R inhibition activity [47][48][49] . Inhibition of 5α-R precludes the conversion of testosterone to dihydrotestosterone (DHT) high levels of which are associated with BPH [50] . ...
... The prostate wet weight was calculated as the prostate weight/body weight ratio as described by Nahata. 19 The size of the prostate was measured using a 1 mm precision sliding caliper (IGAGING ® ) and prostate volume was calculated using the formula of Rahul 20 : volume = length  weight  height  π/6. The percentage (%) of tumor incidence in each group was obtained by using the formula: % tumor incidence = (number of apparent prostate tumor/number of rats)  100. ...
Despite enormous progress in modern medicine, prostate cancer (PCa) remains a major public health problem due to its high incidence and mortality. Although studies have shown in vitro antitumor effects of cucurbitacins from Cucumis sativus, the in vivo anticancer effect of the seed oil as a whole, has yet to be demonstrated. The present study evaluated the in vitro anticancer mechanisms of C. sativus (CS) seed oil and its possible chemopreventive potential on benzo(a)pyrene (BaP)-induced PCa in Wistar rat. In vitro cell growth, clone formation, cell death mechanism, cell adhesion and migration as well as expression of integrins β-1 and β-4 were assessed. In vivo PCa was induced in 56 male rats versus 8 normal control rats, randomized in normal (NOR) and negative (BaP) control groups which, received distilled water; the positive control group (Caso) was treated with casodex (13.5 mg/kg BW). One group received the total seed extract at the dose of 500 mg/kg BW; while the remaining three groups were treated with CS seed oil at 42.5, 85, and 170 mg/kg BW. The endpoints were: morphologically (prostate tumor weight and volume), biochemically (total protein, prostate specific antigen (PSA), oxidative stress markers such as MDA, GSH, catalase, and SOD) and histologically. As results, CS seed oil significantly and concentration-dependently reduced the DU145 prostate cancer cell growth and clone formation (optimum = 100 μg/mL). It slightly increased the number of apoptotic cells and inhibited the migration and invasion of DU145 cells, while it decreased their adhesion to immobilized collagen and fibrinogen. The expression of integrin β-1 and β-4 was increased in presence of 100 μg/mL CS oil. In vivo, the BaP significantly elevated the incidence of PC tumors (75%), the total protein and PSA levels, pro-inflammatory cytokines (TNF-α, IL-1, and IL-6) and MDA levels compared to NOR. CS seeds oil significantly counteracted the effect of BaP by decreasing significantly the PC incidence (12.5%), and increasing the level of antioxidant (SOD, GSH, and catalase) and anti-inflammatory cytokine IL-10 in serum. While in BaP group PCa adenocarninoma was the most representative neoplasm, rats treated with 85 and 170 mg/kg prevented it in the light of the casodex. It is conclude that CS may provide tumor suppressive effects in vitro and in vivo which makes it an interesting candidate to support the current treatment protocol.
... Seks hormonlarının etkilerinin inhibe edilmesi, prostat hücre metabolizmasının baskılanması ve antienflamatuvar etkileri nedeniyle günümüzde BPH tedavisinde kullanılmaktadır (39). Urtica dioica' dan elde edilen β-Sitosterol ve skopoletin moleküllerin testosterona bağımlı BPH'nin tedavisinde kullanılabileceği fareler üzerinde moleküler düzeyde gösterilmiştir (48). ...
Prostata bağlı rahatsızlıkların en yaygın olanları prostatit, prostat kanseri ve iyi huylu prostat hipertrofisi (BPH) dir. Tedavi amacıyla kullanılan fitoterapötik bitkilerin doğal olduğu ve bu nedenle yan ektilerinin olmadığı düşüncesi, kolay ulaşılabilir olması, bu ürünler üzerine yapılan yoğun reklam faaliyetleri, online ticaret gibi sebeplerle tıbbi bitkilere olan son yıllarda yoğunlaşmıştır. Prostat sorunlarında, Amerika’da yaklaşık 2,5 milyon kişinin bitkileri kullandığı, batı ülkelerinde özellikle Almanya’da hekimlerin fitoterapiyi birinci sırada tercih ettiği rapor edilmiştir. Erkeklerin 1/3’nin bitkisel tedaviyi tek başına veya kombine tedavi olarak uyguladığı belirlenmiştir.
... Estimation of prostate/body weight proportion, week by week pee result and serum testosterone levels, prostate-explicit antigen levels (on day 28) and histological assessments completed prompted reason that U. dioica can be utilized as a viable medication for the administration of BPH. These impacts are connected with two biochemical markers, β-sitosterol and scopoletin (Nahata and Dixit, 2002) (Asgarpanah J. and Mohajerani R. 2012). Table 1. ...
present book focuses upon the Trends and Innovations in
Humanities, Management, Commerce, Science and Technology. Humanities,
Management, Commerce, Science and Technology are the key drivers for
economic growth and human development. For India to march ahead on a
sustainable development pathway to include economic development, social
inclusion and environmental sustainability for achieving an Atmanirbhar
Bharat'', a greater emphasis will be given on promoting traditional knowledge
system, developing indigenous technologies and encouraging grass root
innovation. The emergence of disruptive and impactful technologies poses new
challenges and simultaneously greater opportunities. The COVID-19 pandemic
provided a compelling opportunity for Research and Development institutions,
academia and industry to work in unison for sharing of purpose, synergy,
collaboration and cooperation. Innovations in Humanities,
Management, Commerce, Science and Technology will to bring about profound
changes through short-term, medium-term, and long-term mission mode
projects by building a nurtured ecosystem that promotes research and
innovation on the part of both individuals and organizations. It will identify and
address strengths and weaknesses of the Indian Innovations in Humanities,
Management, Commerce, Science and Technology ecosystem to catalyse socioeconomic
development of the country and also make the Indian Innovations in
Humanities, Management, Commerce, Science and Technology ecosystem
globally competitive. In this book we have covered all the related to Trends and
Innovations in Humanities, Management, Commerce, Science and Technology
issues.
... UD contains such compounds as sterols, flavonoids, and polysaccharides, which may have antiandrogenic effects and prevent the formation of active forms of testosterone by inhibiting 5-alpha reductase activity. Thus, stromal cells and follicular cell orders are preserved through normal functioning levels, thereby enhancing fertility power (33). Aktas et al showed that the structural disorders were reduced in the group administered with 2 mg/kg UD during spermatogenesis (34). ...
Background: Urtica dioica (UD), as a natural antioxidant, has positive effects on oocyte maturation. This study aimed to investigate the effects of hydro-alcoholic UD extract and retinoic acid on follicular development in an in vitro fertilization (IVF) condition.
Methods: A total of 40 female Wistar rats were randomly divided into 5 groups: group 1 received normal saline, group 2 was given 25 mg/kg retinoic acid, group 3 was administered with 100 mg/kg UD extract, group 4 was treated with retinoic acid plus UD extract, and group 5 received 10 mg/kg olive oil. The histomorphometric parameters were analyzed, including the number of follicles, follicular atrophy, fertilized oocytes, 2-cell embryos, dead embryos, and blastocysts.
Results: Retinoic acid caused a significant increase in the primary, preantral, and atretic follicles and a substantial decrease in the corpus luteum compared with the control group (p<0.001). The number of preantral, antral follicles, and corpus luteum was significantly higher in group 3 compared with group 1 (p<0.001). Moreover, coadministration of UD plus retinoic acid (group 4) significantly reduced the atretic follicles (p<0.05).
Conclusion: Based on the results, UD herbal extract, as a natural antioxidant agent, could reduce the adverse effects of retinoic acid on oocyte maturation in an IVF condition.
... During BPH condition patients feels discomfort during urination. It is reported that basically stinging nettle prevents conversion of testosterone into dihydrotestosterone and thus decreases size of prostate gland [13][14] . Other than these stinging nettles are also used to treat hay fever. ...
When we take protein rich meal then protein is used in formation of
various amino acids. During synthesis of amino acids creatinine is produced
that is stored in muscles in the form of creatine. During muscle functioning
Creatine gets phosphorylated and creatinine is produced as byproduct. If our
kidneys function normally then they can filter creatinine out. But this is bit
problematic when our kidneys are not functioning well or as an another
reason intake of protein rich meals and creatinine supplements leads higher
level of creatinine than its normal range. If person has high blood pressure,
diabetes, Urinary Tract Infection, using more diuretics and antihypertensive
drugs then these also increases creatinine level. Present chapter emphasizes
primary functional aspects of certain useful botanicals like Beet Root, Garlic,
Green Tea, Astragalus & Stinging Nettles and by taking personal care in
regular diet can decrease blood serum creatinine level significantly. These all
trials with medications suggested by medical officers can decrease creatinine
level in person with normal functioning kidneys and are also proven to be
helpful in patients suffering from Chronic Kidney Disease (CKD). At the
end purpose of these trials is only to keep patient away from dialysis and
other long term treatments
... A decrease in serum testosterone levels, urine output per week, and body weight/prostate ratio were observed. These studies strongly propose that BPH can be managed by Urtica dioica [60] . Bazoton uno, Urtica dioica root dry extract, with its anti-proliferative and antiphlogistic properties, reduces the irritative BPH symptoms and associated complications [61] . ...
Urtica dioica (stinging nettle), a flowering plant with the herbaceous perennial habit, belonging to the 'Urticaceae' family, native to temperate Asia, Europe, and North Africa, shows now worldwide distribution. The plant has a long history of being utilized as a medicinal herb. Traditionally, it is being used widely by many medical practitioners to treat many diseases like haematuria, arthritis, nephritis, menorrhagia, and rheumatism. Although this plant's phytochemistry is complex, studies on phytochemical constituents showed the occurrence of compounds like flavonoids, tannins, saponins, proteins, amino acids, and phytosterols. Likewise, Urtica dioica is being used as food, fibre, manure, and cosmetics. The plant also possesses diverse pharmacological activities, including antioxidant, antibacterial, analgesic, antiviral, anti-inflammatory, hepatoprotective, anticancer, and immune-regulatory effects. This review briefs about biological activities, phytochemistry, toxicology, and pharmacology of Urtica dioica.
... Herbal medicine is commonly used as an alternative source of treatment for BPH [10]. A lot of plants with multipharmacological effects in the management of BPH have been scientifically proven for efficacy [11]. ...
Benign prostatic hyperplasia is a progressive pathologic condition common in ageing men, constituting a health burden. Benign prostatic hyperplasia is characterized by the proliferation of prostatic tissues, prostate enlargement, and lower urinary tract symptoms. The use of herbal medicine in the management and treatment of benign prostatic hyperplasia has shown some promise. The efficacy and potency of some polyherbal extracts have been scientifically proven in the management and treatment of diseases, while many others are yet to be investigated. The aim of this study was to determine the effect of the herbal mixture Yagari on experimentally induced benign prostatic hyperplasia in rats and to identify its pharmacologically active agents. The effect of the herbal mixture on experimentally induced benign prostatic hyperplasia in rats was determined using 36 male Wistar rats grouped randomly into 6 groups of 6 rats each. The test rats were treated subcutaneously using a combination of dihydrotestosterone and estradiol valerate in a 10:1 ratio for 28 days according to the standard method. The test rats were thereafter treated with the herbal mixture for 21 days. Prostate-specific antigen, inflammatory cytokines, assay of prostate function hormonal and prostate function enzyme activities, and kidney function test were evaluated in the blood samples collected by ocular puncture applying standard methods. Prostates were harvested and examined for histopathological changes. Biological activity-guided fractionation of Yagari in a silica gel column was carried out and using phospholipase A2 activity as a biomarker. The identity of the bioactive compounds was determined using mass spectroscopy and nuclear magnetic resonance. The herbal mixture showed a positive effect on prostatic hyperplasia by decreasing urinary obstruction through the inhibition of 5-alpha reductase, anti-inflammatory activity, and decreased level of sex hormones. Characterization by spectral studies revealed apigenin (4´,5,7-trihydroxyflavone, molecular weight).
... Estimation of prostate/body weight proportion, week by week pee result and serum testosterone levels, prostate-explicit antigen levels (on day 28) and histological assessments completed prompted reason that U. dioica can be utilized as a viable medication for the administration of BPH. These impacts are connected with two biochemical markers, β-sitosterol and scopoletin (Nahata and Dixit, 2002) (Asgarpanah J. and Mohajerani R. 2012). Table 1. ...
Mucormycosis is an anticonvulsive infection that occurs due to the fungi mucorales and
family Mucoraceae. It is a rare disease but is increasing in immune compromised patients. It
can be categorized into rhino-orbito-cerebral, cutaneous, disseminated, gastrointestinal and
pulmonary types. Mucor mole is found in soil, bread and decaying fruits and vegetables. Leukemia, lymphoma, immuno compromised state, burns and open wound are the risk factors
of mucormycosis. It is classified into 6 main types based on the part of the body that is
af ected. Headache, pain in face, blocked nose, swollen and bulging of eyes, loss of vision, brain damage and death are the main symptoms of mucormycosis. Mucormycosis can be
prevented by wearing mask, avoiding direct contact with soil and contaminated water. This
review mainly focuses on the overview of mucormycosis, itís etipathogenesis, preventive
strategies, advances in diagnosis and the current treatment metho
... Estimation of prostate/body weight proportion, week by week pee result and serum testosterone levels, prostate-explicit antigen levels (on day 28) and histological assessments completed prompted reason that U. dioica can be utilized as a viable medication for the administration of BPH. These impacts are connected with two biochemical markers, β-sitosterol and scopoletin (Nahata and Dixit, 2002) (Asgarpanah J. and Mohajerani R. 2012). Table 1. ...
The organism adaptation to a specified environment has changed in the past few generations. The prokaryotic and eukaryotic genome has been evolved up to an extent of new traits
induced genome. The restriction, modification, mutagenesis can be performed using the new
bioengineering technology termed as CRISPR. Clustered Regularly Interspaced Palindromic
Repeats (CRISPR) or Cas9 protein is the newest and greatly innovative technology which is
considered to be the most current state of the art method for genomic editing in cell culture
and organism. It is more popular because of its easy design and easy operation. Using this
system, researchers can perform site-directed genome modification at the base level
furthermore, the technology is extremely versatile and allows genome engineering. Cas9
being a programmable gene can cure any disease. Recently the biggest of the work is done in
the field of agriculture with the help of CRISPR editing and that is making disease resistant
plants and modification of any targeted genome of plants is possible. This is leading to
formation of genetically improves plants for the growth of sustainable agriculture
production. Because of this editing breeding of resistant plants have also become extremely
easy and fast, because of this these genes edited plants can be made as a standard method or
tool for new era.
... However, there is less evidence for 5α-reductase and androgen receptor modulation from the plant (Chrubasik et al., 2007). The extractions form the leaves show evidence for immunomodulation in pre-clinical (animal) studies (Chrubasik et al., 2007;Hryb et al., 1995;Nahata and Dixit, 2012). In rats, U. dioica inhibits the cellular proliferation and prostatic hyperplasia induced by testosterone, more specifically in the anterior and ventral lobes (Reza Moradi et al., 2015). ...
Background
: The use of herbal medicine and alternative medicine is reported to be in up to 50% of prescriptions for benign prostate hyperplasia (BPH) in Europe, along with an increased global interest for holistic medicinal approaches. This study aimed to systematically review the published evidence investigating the use of herbal medicines as a treatment for BPH in clinical trials based on PRISMA guidelines.
Methods
: A literature search was conducted using PubMed, Cochrane, Medline, and Scopus databases, including English language clinical trials (Jadad score of ≥ 4) that investigated herbal medicine as a sole intervention, reporting at least one of the following outcomes: International Prostate Symptom Score (IPSS); American Urological Association Symptom Index (AUASI); Maximum Urinary Flow Rate (Qmax); Post-void residual volume (PRV); Prostate volume (PV); Serum Prostatic Specific Antigen (PSA); Quality of Life (QoL) Scores.
Results
: Following article screening, 28 articles were included. The most frequently studied herbs in isolation or in combination were Serenoa repens (54%), Urtica dioica (14%), Cucurbita pepo (14%), lycopene (14%), Pygeum africanum (14%) and Linum usitatissimum (7%). These herbal-based formulations mostly improved the symptoms associated with BPH (IPSS/AUASI, Qmax, PSA, QoL scores, PRV and PV). This review further discusses these herbs and the outcomes, with a focus on the potential mechanisms of action.
Conclusions
: There are limited high quality clinical trials investigating herbal medicine on BPH, where S. repens is significantly more represented than other popular herbs for BPH, such as C. pepo, U. dioica, P. africanum, and lycopene. Although the included studies broadly found positive positive results for standardised outcomes for LUTS and urinary flow, there was great variability in the study designs requires caution in interpretation. As these herbs are supported by in vivo and in vitro studies on potential mechanisms of actions, comparison of efficacy of mono-herbal and poly-herbal approaches, standardized extract based on identification of active constituents, as well as dosage and long-term safety.
... L'estratto etanolico delle radici di ortica contiene principalmente scopoletina e β-sitosterolo a cui è stata attribuita un'attività inibitoria della 5α-riduttasi e della proliferazione cellulare prostatica (28). Tale attività, associata ad un'inibizione dell'aromatasi, è stata riscontrata anche per l'estratto metanolico (29). ...
... Exposure to 1 g/mL of roots methanolic extract during 5 day produces a significant decrease in human prostate carcinoma cells (LNCaP) [70] . In addition, in vitro studies of Nahata and Dixit [71] regarding testosterone-induced rat models of prostatic hyperplasia demonstrated that petroleum ether and ethanolic extracts of the U. dioica roots (28 days, 50 mg/kg, oral treatment) significantly reduced the activity of 5 -reductase enzyme, a key enzyme involved in testosterone metabolism, and the dimension of prostatic hyperplasia. Moreover, dichloromethane extract of U. dioica leaves increased the expression levels of the proapoptotic genes caspase 3 and 9 and reduced the expression of the antiapoptotic gene Bcl-2, which inhibited in turn the growth and proliferation of human prostate cancer cells (PC3) after 48 h of exposure at an IC 50 of 15.54 g/mL [72] . ...
Introduction
Traditional medicine is gaining increasing importance worldwide for the management of various health conditions, including urinary diseases. Little is known about this traditional knowledge among Algerian populations, even though the country is very rich in terms of plant biodiversity and ethnicities. This study explored the beliefs, attitudes, and knowledge used in Algerian traditional ethnopharmacological practices for the treatment of urinary diseases.
Method
Field studies were conducted between June 2017 to July 2020 using face-to-face semi structured interviews with 385 herbalists and traditional practitioners in 13 locations in Algeria.
Results
The results revealed that 134 medicinal plants belonging to 121 genera and 53 families were used as traditional therapy for urinary diseases in Algeria. The most represented botanical families were Lamiaceae, Apiaceae, Asteraceae and Poaceae.
The most cited plant species were Parietaria officinalis, Cucurbita maxima, Hordeum vulgare, Citrus limon, Olea europaea, Herniaria hirsuta, Allium cepa, and Urtica dioica. Nevertheless, on the basis of use reports and use value indices, Citrus limon, Parietaria officinalis, Hordeum vulgare, Allium cepa, Olea europaea, Cucurbita maxima, Herniaria hirsuta, Urtica dioica, and Petroselinum crispum were the most reported plant species.
These species are used alone or in mixtures of two or more ingredients from different origins such as honey, olive oil, and goat milk. Our findings revealed several new therapeutic uses and new medicinal plants that are reported for the first time in the treatment of urinary diseases in Algeria.
Conclusion
This is the first ethnopharmacological study documenting the Algerian traditional uses of herbal remedies for treating urinary diseases. Our findings are relevant for the discovery of novel therapeutical drugs.
... Phytoestrogen plays a role in antagonizing the E2 function [59]. It was reported that nettle extract could prevent the formation of dihydrotestosterone (the active form of testosterone) by inhibiting the enzyme 5-alpha reductase [60]. Nettle root extract could inhibit the aromatase activity, prevent androgen from binding to its receptors, and prevent the conversion of testosterone to estrogen [61]. ...
Background
Polycystic ovary syndrome (PCOS) is one of the most prevalent endocrinopathies in women during the reproductive age. Herbal medicines are used increasingly alone or in supplement with chemical medicines for the treatment of different diseases and dysfunctions. This study was aimed to evaluate the effects of lutein and nettle ( Urtica dioica ) extract on the biochemical parameters and the reproductive function in the PCOS model of mice.
Methods
Following the induction of PCOS by dehydroepiandrosterone (DHEA), the mice ( n = 98) were randomly assigned into seven groups, each consisting of fourteen mice; the groups were included control group (received solvent), PCOS group (received 6 mg/100 g B.W/day IP, DHEA for 21 days), PCOS+ Nettle extract (200 and 400 mg/kg), PCOS+ Lutein (125 and 250 mg/kg), and PCOS+ NL (200 mg/kg nettle extract and 125 mg/kg lutein). The nettle extract and lutein were administrated using gavage for 30 consecutive days after PCOS induction. Malondialdehyde (MDA), total antioxidant capacity (TAC), and estrogen were measured in serum, ovary, and uterus samples by the ELISA method. The total number of oocytes, oocyte quality, fertilization rate, 2-cell blastocyst, and arrested embryos (type I, type II, and type III) were also investigated.
Results
A combination treatment of the nettle and lutein produced the lowest concentration of MDA in comparison to other groups which affected by the PCOS. The lowest level of TAC was observed in the PCOS group without treatment. The number of oocytes, oocyte quality, fertilization rate, and 2-cell blastocyst were significantly higher in the control group, but the lowest values were observed in the PCOS group without any treatment.
Conclusions
The most favorable findings include improving antioxidant capacity, oocyte and embryo quality were observed in the PCOS+ 125 L group.
... Возможности воздействия крапивы двудомной на эректильную функцию заключаются в стимулирующем влиянии ее биологически активных веществ (гликозиды, флавоноиды, каротиноиды, хлорофилл, витамины К, С, В 2 , В 3 , органические кислоты, макро и микроэлементы) на трофику андрогензависимых органов и тканей мужского организма. Экстракт крапивы обладает выраженным про тивовоспалительным, мочегонным, антисептическим, про статотропным эффектами, что позволяет широко его при менять при вторичных эректильных нарушениях, связан ных с воспалительным (простатовезикулит) и дисгормо нальным (доброкачественная гиперплазия предстатель ной железы) генезом ЭД [12]. ...
... Similarly, the prostate-specific antigen levels were monitored, which indicated U. dioica can be used to manage BPH. 163 A 51.4% inhibition of induced growth of ventral prostate gland was exhibited by the adult mouse after applying 20% methanolic extract of U. dioica roots. 164 The methanolic extracts of roots of U. dioica exhibited the inhibitory effect on the enzymes aromatase (AR) and 5a-reductase (5a-RE) in a concentration dependent manner, with ED 50 calculated as 3.58 mg/mL and 14.7mg/mL, respectively. ...
Background
Andropause starts in middle-aged men and affects hormonal balance and behavioral/sexual functions. The aim of the present study was to determine the effects of two Rosa Damascena Mill. (Rosaceae, Rosa) and Urtica dioica L. (Urticaceae, Urtica); in relieving andropause symptoms due to their antioxidant and reproductive properties.
Methods
Animals were allocated into five groups including the young, control vehicle, Rosa, Urtica and Rosa + Urtica groups. Behavioral tests were performed. Sperm parameters and sex hormones were also assessed.
Results
Both extracts, especially in combined form increased preference index and muscle strength and decreased the level of depression significantly. Semen quality increased in the extract-treated groups. Testosterone level was increased significantly in the Rosa + Urtica group in middle-aged animals after 50 days of treatment. luteinizing hormone (LH), follicle-stimulating hormone (FSH), and the level of sex hormone binding globulin (SHBG) also changed in the extract-treated groups.
Conclusions
Rosa Damascena Mill and Urtica dioica can change testosterone level in the middle-aged animals and also ameliorate andropause symptoms. Mood, muscle strength and cognition would improve following administration of these herbs. The herbal nature of these extracts and their worldwide use in traditional medicine make them more appropriate for human studies and applications.
A new lignan named (-)-ginkgool-9-O-β-glucopyranoside (1) together with eight known lignans (2-9) were isolated from Urtica triangularis subsp. pinnatifida (Hand.-Mazz.) C.J.Chen. According to the mass spectrometry and spectroscopic analyses, the gross structure and absolute configuration of the new lignan were elucidated. The cytotoxic effects of compounds 1-9 on BPH-1 cells and the docking results on type II 5α-reductase were analysed to evaluate their anti-BPH activity. The results showed better anti-BPH activity that compound 4 displaying an IC50 of 79.75 ± 3.68 μM than finasteride presenting an IC50 of 91.8 ± 3.74 μM. Compounds 1, 2 and 5 had moderate anti-BPH activity compared with finasteride.
Phytosterols are bioactive substances that are found spontaneously in the cell membranes of plants and have an atomic composition similar to cholesterol produced by vertebrate cells. They are widely distributed in dietary lipids from plants such as nuts, seeds, and beans with olive oil. β-sitosterol has a variation of pharmacological belongings, with analgesic, immunomodulatory, antiseptic, antineoplastic, anti-inflammatory, cholesterol decreasing, hepatoprotective, and protecting action concerning respiratory and non-alcoholic fatty liver disease illnesses, antioxidant, and anti-diabetic activity. Clinical studies on humans have shown that it works against prostate cancer and has anti-inflammatory and anti-cancer properties. Pharmacological testing of β-sitosterol demonstrated a range of actions including antibacterial, anti-inflammatory, antinociceptive, anticancer, antifertility, angiogenic, antioxidant, immunomodulatory, diabetes-fighting, and anticancer without significant toxicity. Several formulations have been created by numerous authors, but there are few scholarly reviews of the analytical, pharmacology, and phytochemistry methodologies for this molecule. In this review the literature on β- sitosterol, its biosynthesis, pharmacology, nutraceutical applications, toxicity, formulations, and analytical techniques are all highlighted.
Aim:
This study purposed to evaluate the modulator and protective role of Urtica dioica (UD) extract against deleterious effects of retinoic acid (RA) high doses on histological parameters and fertilization of rats.
Materials and methods:
For the in-vivo phase, 60 female Wistar rats were divided into 6 identical groups as 1) control, 2) 25 mg/kg RA, 3) 25 mg/kg UD extract, 4) 50 mg/kg UD extract, 5) UD extract (25 mg/kg) + RA (25 mg/kg), and 6) UD extract (50 mg/kg) + RA (25 mg/kg). Biochemical parameters, including luteinizing hormone (LH), folliclestimulating hormone (FSH), malondialdehyde (MDA) levels, superoxide dismutase (SOD), and catalase (CAT) activities, were measured. In the in-vitro phase, oocytes were obtained from 10 female rats without injection. In addition to the mentioned parameters, histological parameters (oocytes in various stages) and the results of IVM, IVF, and embryo developments were assessed and compared among the groups with the use of one-way ANOVA and Tukey's post hoc tests.
Results:
The high dosage of RA significantly reduced the LH and FSH levels; however, UD alone and with RA increased the hormone levels in rats. Regarding the reactive oxygen species (ROS) activity levels in rats' blood samples, RA increased the MDA and decreased the SOD and CAT levels. Treatment with UD extract (UD + RA groups) significantly improved the parameters mentioned, showing UD's antioxidant effect. The rate of oocyte maturation, 2-cell-4-cell and 4-cell-8-cell embryos, and blastocyst formation increased significantly in the groups in which UD extracts were administered compared to the control and RA groups. Furthermore, the increases were significant in the UD + RA groups compared to the RA group.
Conclusion:
UD extract can significantly reduce RA high doses side effects on histological parameters and fertilization of rats and has the protective potential against RA deleterious effects.
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Cilt hastalıkları
Ürolojik hastalıklar
Benign prostatic hyperplasia (BPH) is an enlargement of the prostate gland caused by progressive hyperplasia, or abnormal growth of cells of the glandular epithelial and stromal cells. Globally, it has been documented that more than 80% of men by the age of 80 will suffer from BPH. Most men are hesitant to undergo surgical interventions for fear of losing potency and the perception of other adverse side effects. Effectto® is a polyherbal formulation designed by Vasu Research Center to be used for the treatment of BPH. It can also be indicated that it can be used for lower urinary tract symptoms and bladder outlet obstruction. The formulation is expected to provide significant BPH relief. The present study was planned to evaluate the effect of a polyherbal formulation on testosterone- and citral-induced Prostatic Hyperplasia. The activity of the polyherbal formulation for BPH was evaluated using testosterone depot injection as the inducing agent in a testosterone-induced model and citral-induced model for the atypical type of BPH in rats. Also, the acute toxicity study was done using OECD 423 guidelines to check the toxicity of the test compound. Data are expressed as mean ± SD and statistical significance was evaluated using one way ANOVA followed by Tukey’s multiple comparison tests. The polyherbal formulation was found to be safe at oral doses of 2000 mg/kg. Effectto® significantly decreased the weight of the prostate in the testosterone model as well as the citral model in rats. The effect on biochemical markers like serum PSA and TNF-α was also seen in both the cases. In particular serum PSA, the decrease was majorly significant in both the models when XIII compared. The formulation was able to reverse the effect of inducing agents on the prostate’s size.
Background
Benign prostatic hyperplasia is one of the most common benign tumor in men. Due to frequent side effects associated with medications used to treat prostatic hyperplasia, the use of herbal plants such as nettle has increased for the management of this ailment.
Purpose
The purpose of the present study was to determine the effect of nettle root extract on urinary problems, prostatic specific antigen level, and prostate volume in older men with benign prostatic hyperplasia.
Study Design
The present study was a randomized clinical trial.
Methods
This study was conducted on 80 participants with benign prostatic hyperplasia referred to a urology clinic in Kashan, Iran. The participants were randomly assigned into experimental (n= 40) and control (n= 40) groups. The participants in the experimental and control groups received a tablet containing 300 mg of nettle root extract or a placebo (starch), respectively, twice a day for eight weeks. Before and after the intervention, the participants were assessed regarding their prostatic specific antigen level, prostate volume, and the American Urological Association Symptoms Scores associated with urinary problems. Data was analyzed using the Fisher’s exact test, the Chi-square test, the Paired t-test, and the independent samples t-test.
Results
After the intervention, there were significant differences between the groups in terms of urinary frequency (control: -0.17 ± 0.74 versus experimental: -0.5 ± 0.67; p= 0.04), urinary urgency (control: 0.12 ± 0.91 versus experimental: -0.32 ± 0.69; p= 0.01), and nocturia (control: 0.0 ± 0.65 versus experimental: -0.28 ± 0.64; p= 0.05). The group comparisons showed that there was no significant difference between the groups in terms of changes in the prostate-specific antigen level (p= 0.44), prostate volume (p= 0.22), feeling of incomplete emptying (p=0.72), intermittency (p=0.26), weak urine stream (p=0.44), straining (p= 0.85), and quality of life (p= 0.91) associated with urinary problems.
Conclusion
The use of nettle root extract in combination with conventional medical treatment of BPH was effective in decreasing the severity of urinary problems, including urinary frequency, urgency, and nocturia in participants. However, the nettle extract was not effective in modifying prostate-specific antigen level, prostate volume, feeling of incomplete emptying, intermittency, urine stream, straining, and quality of life associated with urinary problems. Nettle extract is recommended for use as a complementary intervention along with traditional medical treatments of benign prostatic hyperplasia.
Background
Benign prostatic hyperplasia (BPH) is one of the most common causes of lower urinary tract symptoms (LUTS) in older men. Nowadays, there are several plant extracts used for the treatment of LUTS due to BPH.
Objective
The aim of this study is to compare the effect of combining silodosin 8 mg with Serenoa repens, Urtica dioica, Cucurbita pepo (Rotaprost 530 mg) compared to silodosin 8 mg and Rotaprost 530 mg alone in patients with LUTS/BPH.
Methods
Four hundred five men with symptomatic BPH were recruited for the study from June 2020 to January 2021. Three hundred eighty-nine patients were followed up for 6 months. All participants provided written informed consent. This prospective study included analysis of three treatment groups: Group I patients (n = 130) received a combination of silodosin 8 mg and Rotaprost 530 mg (containing a dry extract of Serenoa repens 80 mg, a dry extract of Urtica dioica 150 mg, a dry extract of Cucurbita pepo seeds 200 mg, zinc (in the form of zinc picolinate) 0.105 mg, and selenium (as sodium selenite) 22.5 µg); the group II (n = 129) received silodosin 8 mg alone, and the group III (n = 130) received Rotaprost 530 mg alone. Outcomes were measured by changes from baseline in International Prostate Symptom Score (IPPS) total score, PSA value, prostate volume, residual urine after urination, and maximum flow rate. Statistical significance was set at P < 0.05.
Results
In group I, IPSS, prostate volume, and maximum urinary flow rate (Qmax) improved significantly (P < 0.05) compared with groups II and III during follow-up. Prostate volume in group I showed a significant decrease only during 6 months of therapy (P < 0.05). No serious adverse effects were registered in the three groups.
Conclusion
Combination therapy with silodosin 8 mg significantly reduced LUTS/BPH, Qmax, and prostate volume compared with silodosin 8 mg alone. Rotaprost 530 mg can also reduce PSA by at least 20.6−25.7% after 6-months of treatment.
The objective of the present work included the evaluation of the antioxidant action of Iraqi propolis extract in vivo and in vitro. The in vitro part of the study comprised studying the scavenging activity of serial concentrations of propolis extract in two different methods DPPH scavenging assay and reducing power assay. Results showed that IC50 of the propolis extract, and the reference drug (ascorbic acid) with regard to the DPPH scavenging activity, were 1.65µg/mL, 1.74 respectively while 1.08 µg/ml and 1.11 µg/ml regarding the reducing power assay respectively. The in vivo part involved studying the antioxidant and therapeutic activity of 200mg/ kg BW of propolis extract given twice daily on the exogenous testosterone-induced benign prostatic hyperplasia (TIBPH) in the wister rat which was conducted on 18 male rats divided randomly into the 3 groups of 6 rats for each group. After completion of treatment Prostate weight, prostate index, Malondialdehyde (MDA) content, catalase (CAT) activity, glutathione (GSH) content, and superoxide dismutase (SOD) activity markers were measured. Results showed a significant (P<0.05) improvement in different mentioned parameters of propolis treated rats included a reduction in both prostatic weight and prostatic index, decrease in MDA content with significant (P<0.05) increase in GSH content, CAT and SOD activities as compared with a positive control group. In conclusion, the above results proved that propolis has good therapeutic and antioxidant activities against (TIBPH) in rats.
The objective of the present work included evaluation of antioxidant action of Iraqi propolis extract in vivo and in vitro. The in vitro part of the study comprised studying of the scavenging activity of serial concentrations of propolis extract in two different methods DPPH scavenging assay and reducing power assay. Results showed that IC50 of the propolis extract, and the reference drug (ascorbic acid) with regard to the DPPH scavenging activity, were 1.65µg/mL, 1.74 respectively while 1.08 µg/ml and 1.11 µg/ml regarding to the reducing power assay respectively. The in vivo part involved studying the antioxidant and therapeutic activity of 200mg/ kg BW of propolis extract given twice daily on the exogenous testosterone induced benign prostatic hyperplasia (TIBPH) in the wister rat which conducted on 18 male rats divided randomly to the 3 groups of 6 rats for each group. After completion of treatment Prostate weight, prostate index, Malondialdehyde (MDA) content, catalase (CAT) activity, glutathione (GSH) content, and superoxide dismutase (SOD) activity markers were measured. Results showed a significant (P<0.05) improvement in different mentioned parameters of propolis treated rats included reduction in both prostatic weight and prostatic index, decreased in MDA content with significant (P<0.05) increase in GSH content, CAT and SOD activities as compared with positive control group. In conclusion, the above results proved that the propolis have a good therapeutic and antioxidant activities against (TIBPH) in rats.
Benign prostatic hyperplasia (BPH) is a common chronic disease in ageing men. Synthetic inhibitors of 5α‐reductase commonly used in BPH treatment have limited effectiveness and may cause side effects. Evaluation of iodised serum milk protein and lycopene therapeutic effect in rat BPH model was the aim of the present study. BPH was induced in male Wistar rats by surgical castration and subsequent testosterone administrations (25 mg/kg, 7 injections). Rats with induced BPH received lycopene (5 mg/kg), iodised serum milk protein (200 µg/kg) or their combination for 1 month daily. The efficacy of the treatment was evaluated by the prostate weight, prostatic index and ventral lobe epithelium thickness. In lycopene and iodised serum milk protein‐treated rats, prostate weight and prostatic index were significantly reduced compared to control group; and lycopene and iodised serum milk protein used in combination yielded an additive effect. Thus, further investigation of combined supplementation with micronutrients and plant‐derived substances in BPH models may help to find new opportunities or its safe and effective treatment.
Several medicinal plants are traditionally used in different regions of Africa for the treatment of male infertility, sexual asthenia, erectile dysfunction, and impotency or used as an aphrodisiac. Scientific studies, mostly conducted in vitro or in animals, have proven the acclaimed traditional use of these plants to enhance sexual activities or sperm concentration, motility, and viability. Some of the mechanisms of actions associated with these plants include increased level of testosterone and the relaxation of the smooth cavernosal muscles. However, some plants were also shown to have detrimental effects on the male reproductive system. This may be due to the varying modes of plant extraction, duration of treatment, experimental design, dosage used, quality of the plant, or toxic effects. There is a need to standardize the protocols as well as to better understand the mechanism of actions of the respective plants. Further studies should be conducted using human subjects.
Pycnogenol, produced from Pinus pinaster (French maritime pine) extractions, is a significant source of medicinal procyanidins with OS and immune-modulating properties. Limited studies suggest a role in protection against induced spermatotoxicity through improved OS markers, and may improve fertility outcomes of subfertile males. However, the most significant clinical indication of this combination has been demonstrated for erectile dysfunction. Urtica dioica (stinging nettle) contains numerous molecules relevant to human health, including various polyphenols, triterpenoids, sterols, flavonoids, lectins, and fatty acids. Mechanisms of action relevant to the clinical indications include antioxidant and anti-inflammatory activity, alongside 5α-reductase and aromatase inhibition, and antiproliferative and cell cycle arrest in cancers. Preclinical studies have shown benefit in both BPH and prostate cancer cell lines, and the prevention of diabetes-induced reproductive dysfunction. Clinical studies predominantly combine U. dioica with Sabel serrulata (saw palmetto) in BPH-induced LUTS. This combination has shown benefit in numerous clinical trials particularly in IPSS scores, improved residual volume, peak, and maximal urinary flow rates. This chapter reviews the current preclinical and clinical evidence for these herbal medicines in andrology.
Urtica dioica L. (nettle) has been widely used in industry, cosmetics and medicine and has long been used by the public in
phytotherapeutic applications. Despite its economic potential, it is still not cultivated but consumed as wild. In this study, total phenolic
and flavonoid content, antioxidant and antimicrobial activities of nettle extracts obtained by different methods were investigated. In this
study, antioxidant and antimicrobial activities of nettle extracts obtained by different methods and the oil content of the extracts was
analyzed by GC-MS. As a result of GC-MS analysis, 12 different fatty acids were determined. The main fatty acid components of nettle
extracts were linoleic acid (61.40%), oleic acid (14.66%) and palmitic acid (10.42%). Ultrasonic bath was found to be more effective in
extracting bioactive contents of extracts than fermentation and water boiling methods. Total phenolic content of plant extracts obtained
by USB method was 26.78 mg g-1, total flavonoid amount was 3.07mg g-1, FRAP value was 21.53 µg g-1and DPPH value was 6.20 mgg-1. According to antimicrobial activity results, ethanol extracts showed a better inhibition effect on bacteria than water extracts, but none
of the extracts were found to be effective against Candida albicans.
Nowadays, androgen-mediated diseases such as prostate cancer, hirsutism, acne, androgenic alopecia and benign prostatic hyperplasia (BPH) have become serious problems. The aim of the present study was to find out whether Ganoderma lucidum (GL) can be used as a clinically effective medicine for the management of prostatic hyperplasia. Materials and Methods: In vitro studies were conducted to assess the 5α-reductase inhibitory potential of GL. Testosterone (3 mg/kg s.c.) was administered to the rats along with the test extracts (10, 20 and 50 mg/ kg p.o for a period of 28 days. Finasteride was used as a positive control (1 mg/ kg p.o.). Results and Discussion: GL extracts attenuated the increase in the prostate/ body weight ratio (P/BW) induced by testosterone. Most of the values were significant when compared to testosterone-treated group and finasteride treated groups. Petroleum ether extract (50 mg/kg p.o.) exhibited the best activity (P<0.01). Ethanolic extract ( 20 and 50 mg/ kg p.o. ) also exhibited significant activity ( P<0.01) . The urine output also
improved significantly (P<0.01 in all groups as compared to standard finasteride), which emphasize the clinical implications of the study. Testosterone levels measured weekly and prostate-specific antigen (PSA) levels measured at the end of the study also support the findings. Histological studies indicate significant improvement in the prostatic histoarchitecture in the extract-treated groups as compared to the testosterone-treated group. Conclusion: Study clearly reflects the utility of extracts in BPH. Because of conversion of testosterone to dihydrotestosterone, the prostate size is increased, thereby causing obstruction in urinary output. The observed effect that extracts do not allow the increase as reflected by urinary output, P/BW ratios and histoarchitecture showed that activity of administered testosterone was blocked by the extract and resulted in recovery.
The present study determined the anti-inflammatory activity and related mechanisms of scopoletin. It was found that scopoletin significantly inhibited croton oil-induced mouse ear edema. Scopoletin could also decrease the vascular dye leakage induced by topical application of croton oil, consistent with the reduced myeloperoxidase (MPO) activity and polymorphonuclear (PMN) infiltration. The inhibitor of nitric oxide (NO) synthase l-Nω -nitro-arginine (l-NN, 10 mg/kg) attenuated croton oil-induced ear edema by 56.5%. However, pretreatment of l-NN did not affect the inhibitory effects of scopoletin (100 mg/kg) on mouse ear edema, which suggested that scopoletin exerted anti-inflammatory activities in an endothelial NO-independent manner. Further research revealed that scopoletin reduced the overproduction of PGE2 and TNF-α in croton oil-treated mouse ears. Scopoletin was also shown to attenuate the hind paw edema induced by carrageenan in mice, and lower the MPO activity and malondialdehyde (MDA) level in paw tissues. These findings imply that the anti-inflammatory activities of scopoletin involve inhibition of eicosanoid biosynthesis, cell influx, and peroxidation.
Male hypogonadism is a condition in which the body does not produce enough of the testosterone hormone; the hormone that plays a key role in masculine growth and development during puberty. There is a clear need to increase the awareness of hypogonadism throughout the medical profession, especially in primary care physicians who are usually the first port of call for the patient. Hypogonadism can significantly reduce the quality of life and has resulted in the loss of livelihood and separation of couples, leading to divorce. It is also important for doctors to recognize that testosterone is not just a sex hormone. There is an important research being published to demonstrate that testosterone may have key actions on metabolism, on the vasculature, and on brain function, in addition to its well-known effects on bone and body composition. This article has been used as an introduction for the need to develop sensitive and reliable assays for sex hormones and for symptoms and treatment of hypogonadism.
Background:
Benincasa hispida Cogn. has been used traditionally in India for the management of urinary disorders. The fruit of B hispida is used as a diuretic and the seeds have been reported to possess antiangiogenic effects in prostate cells.
Objective:
The aim of the present study was to examine the effect of petroleum ether extract, ethanolic extract, and B hispida seed oil on hyperplasia of the prostate induced by the subcutaneous administration of testosterone in rats.
Methods:
In vitro studies were performed to determine the 5α-reductase inhibitory potential of the extracts. The results of those studies paved the way for the pharmacologic screening of the extracts to assess their potential against testosterone-induced hyperplasia in rats. Nine groups containing 10 rats per group were created for this study. Hyperplasia was induced by administration of testosterone (3 mg/kg SC) for 14 days in all the groups except the vehicle-treated group. Simultaneous administration of petroleum ether extract (100 or 200 mg/kg PO), ethanolic extract (100 or 200 mg/kg PO), and B hispida seed oil (20 or 40 mg/kg PO) was conducted. A standard 5α-reductase inhibitor (ie, finasteride) was used as a positive control. The weight of the rats was recorded on day 0 (ie, day 1 of the study) and on day 14, and the influence of testosterone and test extracts on the weight of the rats was determined. On day 14, rats were euthanized; prostates were dissected out, and weighed. The rats' prostate/body weight (P/BW) ratio was then determined. Histologic examinations were performed on prostates from each group.
Results:
The petroleum ether extract as well as B hispida seed oil exhibited inhibition of 5α-reductase activity in in vitro studies. Ethanolic extract did not exhibit significant inhibitory potential in vitro. Further in vivo study found that testosterone treatment significantly increased the rats' P/BW ratio in all the groups except the vehicle-treated rats, and this increase in weight was significantly inhibited in rats administered petroleum ether extract (100 and 200 mg/kg PO) and B hispida seed oil (20 and 40 mg/kg PO). Ethanolic extract did not exhibit any significant activity.
Conclusions:
Petroleum ether extract and B hispida seed oil inhibited testosterone-induced hyperplasia of the prostate in these rats. Further studies are needed to evaluate its effect in humans with benign prostatic hyperplasia.
The petroleum ether extract of Citrullus colocynthis Schrad (Cucurbitaceae) fruits and a steroidal compound isolated from this extract were tested in Wistar rats for their effect on Prostatic Hyperplasia (PH) induced by testosterone. The PH was induced in rats by daily subcutaneous injection of testosterone for 10 days. Rats of the test group were administered 100 mg/kg of petroleum ether extract of Citrullus colocynthis fruit along with testosterone. Graded doses i.e, 1, 2.5, and 5 mg/kg dose of isolated steroidal fraction were also tested in three groups of rats. Finasteride was used as positive control. Treatment with C. colocynthis extract reduced prostatic weights of the treated animals considerably. The isolated steroidal fraction also diminished the weight of prostate in dose dependent fashion. Histological examination of prostate revealed that the extract as well as isolate brought a significant change in histo-architecture. The epithelial cells of the treated groups were less involuated and reduction in connective tissue was observed. The petroleum ether extract as well as the isolate exhibited inhibition of 5-alpha reductase activity in in vitro studies. The histological studies, as well as in vitro enzyme inhibitory activity, clearly establish petroleum ether extract and isolate as a potential candidate in management of androgen dependent conditions like benign prostate hyperplasia.
Monoclonal antibodies were raised against prostate-specific antigen (PSA) by immunization with purified free PSA, i.e. not in complex with any protease inhibitor (F-PSA) and PSA in complex with alpha1-anti-chymotrypsin (PSA-ACT). Epitope mapping of PSA using the established monoclonal antibody revealed a complex pattern of independent and partly overlapping antigenic domains in the PSA molecule. Four independent antigenic domains and at least three partly overlapping domains were exposed both in F-PSA and in the PSA-ACT complex, while one antigenic domain was specific for F-PSA. The different domains contained both continuous and discontinuous epitopes. The combination of antibodies recognizing antigenic domains exposed both in F-PSA and PSA-ACT made it possible to develop several highly sensitive sandwich immunoassays for determination of total PSA, i.e. F-PSA + PSA-ACT, with the same molar response for F-PSA and PSA-ACT. Assays specific for F-PSA (cross-reactivity between F-PSA and PSA-ACT < 1%) were developed by the combination of antibodies recognizing epitopes exposed only in F-PSA and antibodies recognizing epitopes exposed both in F-PSA and PSA-ACT.
Images
Figure 3
Although it is generally accepted that benign prostatic hypertrophy (BPH) is a pathologic condition associated with aging and that its symptoms tend to be progressive, there is only limited clinical research to support these impressions. Several studies of the anatomic development of BPH were performed during the 1920s and 1930s, and some significant clinical data were collected during the 1960s and 1970s concerning the incidence of prostatism and its progression. These studies involved different countries as well as different populations within a given country, and so the patient groups being evaluated may not have been typical of the population as a whole. They consist of autopsy cases, patients with symptoms of prostatism, those having prostatic surgery, etc. However, in spite of the varied conditions, reviewing these studies allows us to get an overall picture of the incidence and natural history of BPH.
S. repens is a low shrubby palm native to the southern regions of North America. Preparations from the fruit have been used in traditional American medicine in the treatment of bladder, urethra and prostate irritations. Today, lipophilic extracts of the S. repens fruit are widely used in the therapy of urological symptoms associated with BPH. The clinical efficacy of these extracts and their good tolerability have been demonstrated in numerous clinical trials, including double-blind studies. Inhibition of 5α-reductase activity, antagonism of dihydrotestosterone binding to androgen receptors, double blocking of cycloxygenase and lipoxygenase pathways are the main mechanisms involved in the antiprostatic effect of the S. repens extracts.
Objective.
—To evaluate measurement of percentage of free prostate-specific antigen (PSA) in serum to improve the specificity of prostate cancer screening in men with serum PSA levels between 4.1 and 10.0 ng/mL.Design.
—Retrospective, nonrandomized analysis using a research assay for measuring free PSA in frozen serum from men with a spectrum of prostate sizes and digital rectal examination results.Setting.
—General community outpatient prostate cancer screening program at a university center.Patients.
—One hundred thirteen men aged 50 years or older, 99% of whom were white, with serum PSA concentrations of 4.1 to 10.0 ng/mL, including 63 men with histologically confirmed benign prostatic hyperplasia, 30 with prostate cancer with an enlarged gland, and 20 with cancer with a normal-sized gland. All study volunteers had undergone prostatic ultrasonography and biopsy.Main Outcome Measures.
—Percentage of free PSA in serum and percentage of free PSA cutoff that maintained at least 90% sensitivity for prostate cancer detection.Results.
—Median percentage of free PSA was 9.2% in men with cancer and a normal-sized gland, 15.9% in men with cancer and an enlarged gland, and 18.8% in men with benign prostatic hyperplasia (P<.001). The percentage of free PSA cutoff was higher in men with an enlarged gland and in those with a palpably benign gland. In men with an enlarged, palpably benign gland, a free PSA cutoff of 23.4% or lower detected at least 90% of cancers and would have eliminated 31.3% of negative biopsies.Conclusions.
—Measurement of percentage of free serum PSA improves specificity of prostate cancer screening in selected men with elevated total serum PSA levels and can reduce unnecessary prostate biopsies with minimal effects on the cancer detection rate; however, further studies are needed to define optimal cutoffs. Final evaluation of PSA screening also must consider the ability of current treatments to improve the prognosis of screen-detected prostate cancer.(JAMA. 1995;274:1214-1220)
Because prostatic surgery is not the treatment of choice for most patients with benign prostatic hyperplasia (BPH), the therapeutic effect of a 160-mg, twice-daily, oral dose of Serenoa repens extract was studied during a 3-month open trial in 505 patients with mild-to-moderate symptoms of BPH. The efficacy of the regimen was evaluated in 305 of these patients. Traditional parameters for quantifying prostatism, such as the International Prostate Symptom Score, the quality of life score, urinary flow rates, residual urinary volume, and prostate size, were found to be significantly improved after only 45 days of treatment. After 90 days of treatment, a majority of patients (88%) and treating physicians (88%) considered the therapy effective. In addition, the serum prostate-specific antigen concentration was not modified by the drug, thus limiting the risk of masking any possible development of prostate cancer during treatment. The incidence of side effects (5%) was low and compares favorably with that reported for existing medical therapies used in BPH patients. The extract of Serenoa repens appears to be an effective and well-tolerated pharmacologic agent in treating the mictional problems accompanying BPH.
The prostate gland depends on androgen stimulation for its development and growth. However, testosterone is not the major androgen responsible for growth of the prostate. Testosterone is converted to dihydrotestosterone (DHT) by the enzyme Δ4, 3 ketosteroid, 5α-reductase in prostatic stromal and basal cells. DHT is primarily responsible for prostate development and the pathogenesis of benign prostatic hyperplasia (BPH). Inhibitors of 5α-reductase reduce prostate size by 20% to 30%. This reduction in glandular tissue is achieved by the induction of apoptosis, which is histologically manifested by ductal atrophy. Inhibition also diminishes the number of blood vessels in the prostate because of a reduction in vascular-derived endothelial growth factor. 5α-Reductase occurs as 2 isozymes, type 1 and type 2, with the prostate expressing predominantly the type-2 isozyme, and the liver and skin expressing primarily the type-1 isozyme. Patients have been identified with deficiencies in the type-2 5α-reductase, but not type 1. Knockout mice with the type-2 5α-reductase demonstrate a phenotype similar to that seen in men with 5α-reductase deficiency. Type-1 5α-reductase knockout male mice are phenotypically normal. Enzymatic activity for 5α-reductase or immunohistochemical detection has been noted in other genitourinary tissues, such as the epididymis, testes, gubernaculum, and corporal cavernosal tissue. Preputial skin predominately expresses the type-1 5α-reductase, whereas stromal cells in the seminal vesicle also express type-2 isozyme. However, epithelial cells in the epididymis, but not surrounding stroma, express type-1 5α-reductase. In addition to influencing prostatic growth, 5α-reductase also influences the expression of neuronal nitric-oxide synthase in the corpus cavernosum. The contribution of DHT in the serum, which is partially derived from type-1 5α-reductase in the liver and the small amount of type-1 5α-reductase in the prostate, may play a role in maintaining prostatic enlargement. Thus, in an effort to increase efficacy of treatment for BPH, clinical trials are under way using new drugs, such as GI-198745 (Glaxo-Wellcome, Research Triangle Park, NC), PNU 157706 (Pharmacia & Upjohn, Peapack, NJ), FR146687 (Fujisawa, Osaka, Japan), and LY 320236 (Lilly, Indianapolis, IN), which inhibit both the type-1 and type-2 5α-reductase.
Medical treatments have become available for benign hypertrophy of the prostate, including alpha-receptor blocking agents and 5-alpha-reductase inhibitors. Drugs derived from plants, for which no precise mechanism of action has been described, are widely used for this purpose in Europe. In a randomised, double-blind, placebo-controlled multi-centre study, 200 patients (recruited between April and October 1993) with symptomatic benign prostatic hyperplasia were treated with either 20 mg β-sitosterol (which contains a mixture of phytosterols) three times per day or placebo. Primary end-point was a difference of modified Boyarsky score between treatment groups after 6 months; secondary end-points were changes in International Prostate Symptom Score (IPSS), urine flow, and prostate volume. Modified Boyarsky score decreased significantly with a mean of -6·7 (SD 4·0) points in the β-sitosterol-treated group versus -2·1 (3·2) points in the placebo group p
Background:
Benign prostatic hypertrophy is the nonmalignant, uncontrolled growth of prostatic epithelial cells and stroma that, left untreated, may lead to difficult urination and other complications. A common treatment of BPH is lipid extract from saw palmetto fruit, and lipid extract from Cuban Royal palm (a palm of the same family) fruit is being studied for this use. One study found that the latter, D-004, at 100 to 400 mg/kg daily prevented prostatic hypertrophy (PH) induced with testosterone (T) in a rat model.
Objectives:
This study comprised 2 experiments in a rat model. The first assessed the effects of different doses of D-004 on T-induced PH; the second investigated the effects of D-004 on PH induced with dihydrotestosterone (DHT).
Methods:
In experiment 1, rats were distributed in 6 groups of 10 rats each. One group received an SC injection of soy oil and oral treatment with Tween 65/water vehicle (negative control). The other 5 groups received an SC injection of T 3 mg/kg daily and oral treatment with vehicle (positive control) or D-004 at 50, 200, 400, or 800 mg/kg daily suspended in vehicle. In experiment 2, rats were distributed in 3 groups of 10 rats each. A negative control group received treatment as in experiment 1. Positive controls received an SC injection of DHT 1.5 mg/kg and vehicle orally. The third group received an SC injection of DHT and oral treatment with D-004 at 800 mg/kg suspended in vehicle. All treatments were given for 14 days. At sacrifice, prostates were removed and weighed. Mean prostatic weights and prostatic/body weight ratios were calculated.
Results:
In experiment 1, in the groups receiving D-004 at 200, 400, or 800 mg/kg daily, prostatic weight was significantly lower compared with the positive control group (P < 0.05, P < 0.01, and P < 0.001, respectively); this effect was not seen in the group receiving 50 mg/kg daily. In the groups receiving D-004 at 400 and 800 mg/kg daily, prostatic/body weight ratio was significantly lower compared with positive controls (both, P < 0.05); this effect was not seen in the groups receiving 50 or 200 mg/kg daily. In experiment 2, prostatic weight and prostatic/body weight ratio in the group receiving D-004 were similar to those of positive controls. Body weight was not affected in any of the groups receiving D-004.
Conclusions:
This study of rats with T- or DHT-induced PH suggests that D-004 at 200 to 800 mg/kg daily administered orally prevents T-induced PH, and that D-004 at 800 mg/kg daily does not prevent DHT-induced PH.
While searching for the antiprostatic active principle of the roots of Urtica dioica we ethanol-precipitated a polysaccharide mixture from an aqueous root extract and obtained chemically defined acidic polysaccharides with molecular masses of 15-210kDa. The chemical structures of these compounds have been determined. Some polysaccharides stimulated T lymphocytes in vitro while others influenced the complement system or triggered the release of TNF-α. The crude polysaccharide extract showed a prolonged antiinflammatory activity in the rat paw edema test for 22 hr, which is comparable to the pharmacological efficacy of indometacin. We have reisolated the isolectin mixture (UDA) originally detected in Urtica roots by Peumans et al. (1984). This mixture displayed immunomodulatory effects on T lymphocytes in a dose-dependent manner. In addition, UDA also directly inhibited cell proliferation and blocked binding of epidermal growth factor to its receptor on a tumor cell line, as determined by a [(125)I]-EGF binding assay. These investigations suggest that Urtica polysaccharides and also the N-acetyl-glucosamine specific lectin UDA play a major role in the antiprostatic activity of the drug and phytopreparations containing it.
To report the results of a double-blind, placebo-controlled trial to evaluate Azuprostat® , a β-sitosterol, in patients with symptoms of outlet obstruction caused by benign prostatic hyperplasia (BPH).
A randomized, double-blind and placebo-controlled clinical trial was conducted to assess the efficacy and safety of 130 mg free β-sitosterol (phytosterol) daily, using the international prostate symptom score (IPSS) as the primary outcome variable. In total, 177 patients with BPH were recruited for 6 months of treatment in 13 study centres. In addition to the relative difference in the IPSS, changes in quality of life, peak urinary flow rate (Qmax ) and post-void residual urinary volume (PVR) were recorded. The drug used in the trial consisted of a chemically defined extract of phytosterols, derived for example from species of Pinus, Picea or Hypoxis, with β-sitosterol as the main component.
There were significant (P<0.01) improvements over placebo in those treated with β-sitosterol; the mean difference in the IPSS between placebo and β-sitosterol, adjusted for the initial values, was 5.4 and in the quality-of-life index was 0.9. There were also significant improvements in the secondary outcome variables, with an increase in Qmax (4.5 mL/s) and decrease in PVR (33.5 mL) in favour of β-sitosterol when adjusted for the changes after placebo.
These results show that β-sitosterol is an effective option in the treatment of BPH.
Objectives
To conduct a systematic review of the evidence for the efficacy of β-sitosterolin men with symptomatic benign prostatic hyperplasia (BPH).Methods
Studies were identified through Medline™ (1966–98), EMBASE™ , Phytodok, the Cochrane Library, bibliographies of identified trials and review articles, and contact with study authors and pharmaceutical companies. Randomized trials were included if: men had symptomatic BPH; plant extract preparations contained β-sitosterols; a control group received placebo or a pharmacological therapy; and treatment duration was ≥30 days. Study characteristics, demographic information, enrolment criteria and outcomes were extracted.ResultsFour trials comprising a total of 519 men met the inclusion criteria. All were double-blind and lasted 4–26 weeks. Three studies used nonglucosidic β-sitosterols and one used a preparation that contained only β-sitosterol-β-d-glucoside. Compared with placebo, β-sitosterolimproved urinary symptom scores and flow measures. For the two studies reporting the International Prostate Symptom Score (IPSS), the weighted mean difference (WMD) against placebo was −4.9 IPSS points (95% confidence interval, CI,−6.3 to−3.5). The WMD for peak urinary flow rate was 3.91 mL/s (95% CI 0.91 to 6.90, four studies) and for residual volume the WMD was −28.62 mL (95% CI−41.42 to−15.83, four studies). β-sitosteroldid not reduce prostate size. The trial using pure β-sitosterol-β-d-glucoside (WA184) showed no improvement in urinary flow measures. Withdrawal rates for men assigned to β-sitosterol and placebo were 7.8% and 8.0% (not significant), respectively.Conclusionβ-sitosterolimproves urological symptoms and flow measures. However, the existing studies are limited by short treatment duration and lack of standardized β-sitosterol preparations. Their long-term effectiveness, safety and ability to prevent the complications of BPH are unknown.
The aim of the present study was to find out whether Ganoderma lucidum (GL) can be used as a clinically effective medicine for the management of prostatic hyperplasia. In vitro studies were conducted to assess the 5α-reductase inhibitory potential of GL. A biochemical marker viz. β-sitosterol was identified and characterised in the extracts utilising high-performance thin-layer chromatography. Testosterone (3 mg kg(-1) s.c.) was administered to the rats along with the test extracts (10, 20 and 50 mg kg(-1) p.o.) and β-sitosterol (10 and 20 mg kg(-1) p.o.) for a period of 28 days. Finasteride was used as a positive control (1 mg kg(-1) p.o.). GL extracts attenuated the increase in the prostate/body weight ratio induced by testosterone. Petroleum ether extract exhibiting the best activity. Ethanolic extract also exhibited significant activity. The urine output also improved significantly, which emphasise the clinical implications of the study. Testosterone levels measured weekly and prostate-specific antigen (PSA) levels measured at the end of the study also support our claims. The PSA levels decreased in the extract-treated groups, indicating their usefulness in the treatment of benign prostatic hyperplasia. Histological studies have shown a considerable improvement in the prostatic histoarchitecture in the extract-treated groups when compared to the testosterone-treated group.
The present study reports the attenuating effect of Sphaeranthus indicus extracts (SI) on prostatic hyperplasia induced by testosterone in albino rats. In vitro studies were conducted to assess the 5α-reductase inhibitory potential of the petroleum ether, ethanolic and aqueous extracts of SI. A biochemical marker, β-sitosterol, was isolated and extracts were characterized utilizing HPTLC. Testosterone (3 mg/kg s.c.) was administered to the rats along with the test extracts and isolated β-sitosterol for a period of 28 days. The weight of the rats, the urine output, serum testosterone concentrations and prostate-specific antigen (PSA) levels were recorded. The prostate/body weight ratio (P/BW) was calculated and histological studies were performed to observe the changes in the histoarchitecture of the prostate. Finasteride was used as a positive control (1 mg/kg p.o.). Sphaeranthus indicus extracts attenuated the increase in the P/BW ratio induced by testosterone in the treated groups. The petroleum ether extract exhibited the best activity, although the ethanol and aqueous extracts also exhibited significant activity. Urine output was also improved significantly, demonstrating the clinical implications of the study. Histological studies, testosterone levels which were measured weekly and PSA levels measured at the end of the study also support claims for the potential use of Sphaeranthus indicus in the treatment of prostatic hyperplasia.
The acute toxicities of the global methanol extract of Solanum ligustrinum (Solanaceae) and the crude steroidal glycoalkaloids mixture were determined. The antipyretic, hypothermic and antiinflammatory activities of aqueous, global methanol, petroleum ether, dichloromethane and methanol extracts and crude steroidal glycoalkaloids mixture of the aerial parts were evaluated. All the extracts and the crude steroidal glycoalkaloids mixture were inactive in the hypothermic activity assay, nevertheless, they showed antipyretic and antiinflammatory activities. Scopoletin and beta-sitosterol 3-O-beta-D-glucoside were isolated and identified from the dichloromethane extract. The impure coumarin fraction showed antipyretic and antiinflammatory activities and beta-sitosterol glucoside exhibited antiinflammatory activity. In the light of the results of several NOE experiments, the H-5 and H-8 signals in the H-1-NMR spectra of scopoletin were reassigned. The methanol global extract yielded a crude steroidal glycoalkaloids mixture with antipyretic and antiinflammatory effects.
The oral administration of finasteride, a 4-aza-steroid inhibitor of 5 alpha-reductase, decreases serum dihydrotestosterone levels, but has little effect on serum testosterone. The current study was designed to assess the effect of finasteride on dihydrotestosterone levels in the prostates of men with benign prostatic hyperplasia. In a double blind, placebo-controlled study, 69 men with symptomatic prostatic hyperplasia were treated with placebo or 1, 5, 10, 50, or 100 mg/day finasteride for 7 days before transurethral resection of the prostate. In the placebo group the mean concentration of prostatic dihydrotestosterone was 10.3 +/- 0.6 nmol/kg (+/- SE), and the mean concentration of testosterone was 0.7 +/- 0.1 nmol/kg. After 7 days of treatment with all doses of finasteride, prostatic dihydrotestosterone declined to 15% or less of control levels, and the testosterone concentration increased in a reciprocal fashion. Compared to the placebo group, there was no significant difference in the mean prostatic dihydrotestosterone level achieved in any of the finasteride-treated groups. However, prostatic dihydrotestosterone levels were lower in the groups receiving higher doses of the drug. In two additional patients, finasteride treatment for 2 days also caused a decrease in prostatic dihydrotestosterone levels. No significant adverse experiences occurred during the study. We conclude that finasteride causes profound decrease in prostatic dihydrotestosterone.
Finasteride, a 4-aza steroid compound, is an orally active inhibitor of the 5 alpha-reductase enzyme. 5 alpha-Reductase is necessary for the metabolism of testosterone (T) to dihydrotestosterone (DHT) and is found in high levels only in certain tissues such as the prostate. Finasteride has been shown to markedly suppress serum DHT levels in man without lowering testosterone levels. In patients with benign prostate hyperplasia (BPH), finasteride was found to decrease prostate volume by a mean of 28% over a period of 6 months, without causing clinically significant adverse effects. DHT appears to be the primary androgen for prostatic growth. Selective inhibition of 5 alpha-reductase by finasteride may provide a novel approach to BPH therapy by reducing prostate size without affecting T-dependent processes such as fertility, muscle strength, and libido. The clinical development of finasteride for the treatment of benign prostate hyperplasia is reviewed.
Benign prostatic hyperplasia (BPH) describes a benign enlargement of the prostate gland that develops in the aging male population. Approximately 50% of 60-year-old men have histologic evidence of BPH. The clinical manifestations of BPH are related entirely to the obstruction of urinary outflow. Benign prostatic hyperplasia produces obstruction to urinary flow by static and dynamic factors. The dynamic component of infravesical obstruction presumably is mediated by the tone of the prostate smooth muscle. Pharmacologic agents that cause relaxation of the prostate may represent an effective therapeutic approach for symptomatic BPH. Organ bath contractile studies have indicated that the contractile properties of prostate adenoma are mediated by alpha1 adrenoceptors. Ten clinical trials evaluating the efficacy of alpha adrenergic blockers for the treatment of symptomatic BPH have been performed in Europe during the past 11 years. Clinical efficacy was observed in 9 of the 10 clinical trials. Randomized, placebo controlled, multicenter clinical trials are currently in progress in the United States to evaluate the efficacy of alpha blockers for the treatment of BPH. Rationale and the clinical experience of alpha adrenergic blockers for the treatment of symtomatic BPH is reviewed in this article.
Medical treatments have become available for benign hypertrophy of the prostate, including alpha-receptor blocking agents and 5-alpha-reductase inhibitors. Drugs derived from plants, for which no precise mechanism of action has been described, are widely used for this purpose in Europe. In a randomised, double-blind, placebo-controlled multicentre study, 200 patients (recruited between April and October 1993) with symptomatic benign prostatic hyperplasia were treated with either 20 mg beta-sitosterol (which contains a mixture of phytosterols) three times per day or placebo. Primary end-point was a difference of modified Boyarsky score between treatment groups after 6 months; secondary end-points were changes in International Prostate Symptom Score (IPSS), urine flow, and prostate volume. Modified Boyarsky score decreased significantly with a mean of -6.7 (SD 4.0) points in the beta-sitosterol-treated group versus -2.1 (3.2) points in the placebo group p < 0.01. There was a decrease in IPSS (-7.4 [3.8] points in the beta-sitosterol-treated group vs -2.1 [3.8] points in the placebo group) and changes in urine flow parameters: beta-sitosterol treatment resulted in increasing peak flow (15.2 [5.7] mL/s from 9.9 [2.5] mL/s), and decrease of mean residual urinary volume (30.4 [39.9] mL from 65.8 [20.8] mL). These parameters did not change in the placebo group (p < 0.01). No relevant reduction of prostatic volume was observed in either group. Significant improvement in symptoms and urinary flow parameters show the effectiveness of beta-sitosterol in the treatment of benign prostatic hyperplasia.
To evaluate measurement of percentage of free prostate-specific antigen (PSA) in serum to improve the specificity of prostate cancer screening in men with serum PSA levels between 4.1 and 10.0 ng/mL.
Retrospective, nonrandomized analysis using a research assay for measuring free PSA in frozen serum from men with a spectrum of prostate sizes and digital rectal examination results.
General community outpatient prostate cancer screening program at a university center.
One hundred thirteen men aged 50 years or older, 99% of whom were white, with serum PSA concentrations of 4.1 to 10.0 ng/mL, including 63 men with histologically confirmed benign prostatic hyperplasia, 30 with prostate cancer with an enlarged gland, and 20 with cancer with a normal-sized gland. All study volunteers had undergone prostatic ultrasonography and biopsy.
Percentage of free PSA in serum and percentage of free PSA cutoff that maintained at least 90% sensitivity for prostate cancer detection.
Median percentage of free PSA was 9.2% in men with cancer and a normal-sized gland, 15.9% in men with cancer and an enlarged gland, and 18.8% in men with benign prostatic hyperplasia (P < .001). The percentage of free PSA cutoff was higher in men with an enlarged gland and in those with a palpably benign gland. In men with an enlarged, palpably benign gland, a free PSA cutoff of 23.4% or lower detected at least 90% of cancers and would have eliminated 31.3% of negative biopsies.
Measurement of percentage of free serum PSA improves specificity of prostate cancer screening in selected men with elevated total serum PSA levels and can reduce unnecessary prostate biopsies with minimal effects on the cancer detection rate; however, further studies are needed to define optimal cutoffs. Final evaluation of PSA screening also must consider the ability of current treatments to improve the prognosis of screen-detected prostate cancer.
The effect of the lipidosterolic extract of Serenoa repens (LSESR) on experimental prostate enlargement was investigated in three groups of rats: shams treated with LSESR (sham rats), castrated animals treated with estradiol and testosterone (castrated rats), castrated animals treated with estradiol/testosterone and treated with LSESR (castrated and treated rats). Following three months of continuous hormonal treatment, the weight of prostates in estradiol/testosterone-treated castrated rats was significantly increased in comparison with sham-operated rats. Such an increase started rapidly, reached a maximum by 30 days and remained at a plateau or slightly declined thereafter. The increase of prostate total weight induced by the hormone treatment was inhibited by administration of LSESR. Indeed, the weight was significantly lower at day 60 and day 90 for the dorsal and lateral regions of the prostate. The weight of the ventral region of the prostate was significantly lower after 30 and 60 days treatment with LSESR. These results demonstrate that administering LSESR to hormone-treated castrated rats inhibits the increase in prostate wet weight. This effect of LSESR may explain the beneficial effect of this extract in human benign prostatic hypertrophy.
To report the results of a double-blind, placebo-controlled trial to evaluate Azuprostat, a beta-sitosterol, in patients with symptoms of outlet obstruction caused by benign prostatic hyperplasia (BPH).
A randomized, double-blind and placebo-controlled clinical trial was conducted to assess the efficacy and safety of 130 mg free beta-sitosterol (phytosterol) daily, using the international prostate symptom score (IPSS) as the primary outcome variable. In total, 177 patients with BPH were recruited for 6 months of treatment in 13 study centres. In addition to the relative difference in the IPSS, changes in quality of life, peak urinary flow rate (Qmax) and post-void residual urinary volume (PVR) were recorded. The drug used in the trial consisted of a chemically defined extract of phytosterols, derived for example from species of Pinus, Picea or Hypoxis, with beta-sitosterol as the main component.
There were significant (P < 0.01) improvements over placebo in those treated with beta-sitosterol; the mean difference in the IPSS between placebo and beta-sitosterol, adjusted for the initial values, was 5.4 and in the quality-of-life index was 0.9. There were also significant improvements in the secondary outcome variables, with an increase in Qmax (4.5 mL/s) and decrease in PVR (33.5 mL) in favour of beta-sitosterol when adjusted for the changes after placebo.
These results show that beta-sitosterol is an effective option in the treatment of BPH.
To conduct a systematic review and, where possible, quantitative meta-analysis of the existing evidence regarding the therapeutic efficacy and safety of the saw palmetto plant extract, Serenoa repens, in men with symptomatic benign prostatic hyperplasia (BPH).
Studies were identified through the search of MEDLINE (1966-1997), EMBASE, Phytodok, the Cochrane Library, bibliographies of identified trials and review articles, and contact with relevant authors and drug companies.
Randomized trials were included if participants had symptomatic BPH, the intervention was a preparation of S repens alone or in combination with other phytotherapeutic agents, a control group received placebo or other pharmacological therapies for BPH, and the treatment duration was at least 30 days.
Two investigators for each article (T.J.W., A.I., G.S., and R.M.) independently extracted key data on design features, subject characteristics, therapy allocation, and outcomes of the studies.
A total of 18 randomized controlled trials involving 2939 men met inclusion criteria and were analyzed. Many studies did not report results in a method that permitted meta-analysis. Treatment allocation concealment was adequate in 9 studies; 16 were double-blinded. The mean study duration was 9 weeks (range, 4-48 weeks). As compared with men receiving placebo, men treated with S repens had decreased urinary tract symptom scores (weighted mean difference [WMD], -1.41 points [scale range, 0-19] [95% confidence interval (CI), -2.52 to -0.30] [n = 1 study]), nocturia (WMD, -0.76 times per evening [95% CI, -1.22 to -0.32] [n = 10 studies]), and improvement in self-rating of urinary tract symptoms; risk ratio for improvement (1.72 [95% CI, 1.21-2.44] [n = 6 studies]), and peak urine flow (WMD, 1.93 mL/s [95% CI, 0.72-3.14] [n = 8 studies]). Compared with men receiving finasteride, men treated with S repens had similar improvements in urinary tract symptom scores (WMD, 0.37 International Prostate Symptom Score points [scale range, 0-35] [95% CI, -0.45 to 1.19] [n = 2 studies]) and peak urine flow (WMD, -0.74 mL/s [95% CI, -1.66 to 0.18] [n = 2 studies]). Adverse effects due to S repens were mild and infrequent; erectile dysfunction was more frequent with finasteride (4.9%) than with S repens (1.1%; P<.001). Withdrawal rates in men assigned to placebo, S repens, or finasteride were 7%, 9%, and 11%, respectively.
The existing literature on S repens for treatment of BPH is limited in terms of the short duration of studies and variability in study design, use of phytotherapeutic preparations, and reports of outcomes. However, the evidence suggests that S repens improves urologic symptoms and flow measures. Compared with finasteride, S repens produces similar improvement in urinary tract symptoms and urinary flow and was associated with fewer adverse treatment events. Further research is needed using standardized preparations of S repens to determine its long-term effectiveness and ability to prevent BPH complications.
To conduct a systematic review of the evidence for the efficacy of beta-sitosterol in men with symptomatic benign prostatic hyperplasia (BPH).
Studies were identified through Medlinetrade mark (1966-98), EMBASEtrade mark, Phytodok, the Cochrane Library, bibliographies of identified trials and review articles, and contact with study authors and pharmaceutical companies. Randomized trials were included if: men had symptomatic BPH; plant extract preparations contained beta-sitosterols; a control group received placebo or a pharmacological therapy; and treatment duration was >/=30 days. Study characteristics, demographic information, enrolment criteria and outcomes were extracted.
Four trials comprising a total of 519 men met the inclusion criteria. All were double-blind and lasted 4-26 weeks. Three studies used nonglucosidic beta-sitosterols and one used a preparation that contained only beta-sitosterol-beta-d-glucoside. Compared with placebo, beta-sitosterol improved urinary symptom scores and flow measures. For the two studies reporting the International Prostate Symptom Score (IPSS), the weighted mean difference (WMD) against placebo was -4.9 IPSS points (95% confidence interval, CI,-6.3 to-3.5). The WMD for peak urinary flow rate was 3.91 mL/s (95% CI 0.91 to 6.90, four studies) and for residual volume the WMD was -28.62 mL (95% CI-41.42 to-15.83, four studies). beta-sitosterol did not reduce prostate size. The trial using pure beta-sitosterol-beta-d-glucoside (WA184) showed no improvement in urinary flow measures. Withdrawal rates for men assigned to beta-sitosterol and placebo were 7.8% and 8.0% (not significant), respectively.
beta-sitosterol improves urological symptoms and flow measures. However, the existing studies are limited by short treatment duration and lack of standardized beta-sitosterol preparations. Their long-term effectiveness, safety and ability to prevent the complications of BPH are unknown.
In Germany, plant extracts are often used in the treatment of early stages of benign prostate hyperplasia (BPH). The effects of different concentrations of the polysaccharide fraction of the 20% methanolic extract of stinging nettle roots (POLY-M) on the cellular proliferation of lymph node carcinoma of the prostate (LNCaP) cells were determined by measurement of the genomic DNA content of the samples. All concentrations of POLY-M showed an inhibitory effect on the growth of the LNCaP cells during 7 days except the two lowest concentrations. The reduced proliferation of POLY-M treated LNCaP cells was significantly (p < 0.05) different from the untreated control. The inhibition was time- and concentration-dependent with the maximum suppression (50%) on day 6 and at concentrations of 1.0E-9 and 1.0E-11 mg/ml. No cytotoxic effect of POLY-M on cell proliferation was observed. The in vitro results show for the first time an antiproliferative effect of Urtica compounds on human prostatic epithelium and confirm our previous in vivo findings.
The prostate gland depends on androgen stimulation for its development and growth. However, testosterone is not the major androgen responsible for growth of the prostate. Testosterone is converted to dihydrotestosterone (DHT) by the enzyme Delta(4), 3 ketosteroid, 5alpha-reductase in prostatic stromal and basal cells. DHT is primarily responsible for prostate development and the pathogenesis of benign prostatic hyperplasia (BPH). Inhibitors of 5alpha-reductase reduce prostate size by 20% to 30%. This reduction in glandular tissue is achieved by the induction of apoptosis, which is histologically manifested by ductal atrophy. Inhibition also diminishes the number of blood vessels in the prostate because of a reduction in vascular-derived endothelial growth factor. 5alpha-Reductase occurs as 2 isozymes, type 1 and type 2, with the prostate expressing predominantly the type-2 isozyme, and the liver and skin expressing primarily the type-1 isozyme. Patients have been identified with deficiencies in the type-2 5alpha-reductase, but not type 1. Knockout mice with the type-2 5alpha-reductase demonstrate a phenotype similar to that seen in men with 5alpha-reductase deficiency. Type-1 5alpha-reductase knockout male mice are phenotypically normal. Enzymatic activity for 5alpha-reductase or immunohistochemical detection has been noted in other genitourinary tissues, such as the epididymis, testes, gubernaculum, and corporal cavernosal tissue. Preputial skin predominately expresses the type-1 5alpha-reductase, whereas stromal cells in the seminal vesicle also express type-2 isozyme. However, epithelial cells in the epididymis, but not surrounding stroma, express type-1 5alpha-reductase. In addition to influencing prostatic growth, 5alpha-reductase also influences the expression of neuronal nitric-oxide synthase in the corpus cavernosum. The contribution of DHT in the serum, which is partially derived from type-1 5alpha-reductase in the liver and the small amount of type-1 5alpha-reductase in the prostate, may play a role in maintaining prostatic enlargement. Thus, in an effort to increase efficacy of treatment for BPH, clinical trials are under way using new drugs, such as GI-198745 (Glaxo-Wellcome, Research Triangle Park, NC), PNU 157706 (Pharmacia & Upjohn, Peapack, NJ), FR146687 (Fujisawa, Osaka, Japan), and LY 320236 (Lilly, Indianapolis, IN), which inhibit both the type-1 and type-2 5alpha-reductase.
To investigate the effect of scopoletin on cell proliferation and apoptosis of PC3 cells.
Cell growth curve, MTT assay, and acid phosphatase activity (ACP) were used to determine cell proliferation. Coomassie brilliant blue assay was used to measure the content of protein in cells. Light microscope, transmission electronmicroscope, and fluorescence microscope were used to observe scopoletin-induced morphological changes. Apoptosis rate and cell cycle distribution were determined by flow cytometry.
The IC50 of scopoletin for inhibiting PC3, PAA, and Hela cell proliferation was (157 +/- 25), (154 +/- 51), and (294 +/- 100) mg/L, respectively. Scopoletin induced a marked time- and concentration-dependent inhibition of PC3 cell proliferation. Scopoletin reduced the protein content and decreased the ACP level in PC3 cells in a concentration-dependent manner. Cells treated by scopoletin showed typical morphologic changes of apoptosis by light microscope, fluorescence microscope, and transmission electronmicroscope. Apoptosis rate was 0.3 %, 2.1 %, 9.3 % and 35 % for scopoletin 0, 100, 200, and 400 mg/L, respectively, and cells in G2 phase decreased markedly after being treated with scopoletin.
Scopoletin inhibited PC3 proliferation by inducing apoptosis of PC3 cells.
Phytotherapy of BPS has a long tradition in Germany; nevertheless, data referring to single phytotherapeutic agents are rare. We therefore performed a randomized, double-blind, placebo-controlled multicenter study for 1 year with Bazoton uno (459 mg dry extract of stinging nettle roots) with 246 patients. The IPSS decreased on average from 18.7+/-0.3 to 13.0+/-0.5 with a statistically significant difference compared to placebo (18.5+/-0.3 to 13.8+/-0.5; p=0.0233). The median Q(max) increased by 3.0+/-0.4 ml/s in comparison to 2.9+/-0.4 ml/s (placebo), thus not statistically significantly different, as well as the median volume of residual urine, which changed from 35.5+/-3.4 ml before therapy to 20.0+/-2.8 ml and from 40.0+/-4.0 ml to 21.0+/-2.9 ml under placebo application. The number of adverse events (29/38) as well as urinary infections etc. (3/10 events) was smaller under Bazoton uno therapy compared to placebo. Treatment with Bazoton uno can therefore be considered a safe therapeutic option for BPS, especially for reducing irritative symptoms and BPS-associated complications due to the postulated antiphlogistic and antiproliferative effects of the stinging nettle extract. A strong increase of Q(max) or reduction of residual urine are not to be expected.
The efficacy and tolerability of a fixed combination of 160 mg sabal fruit extract WS 1473 and 120 mg urtica root extract WS 1031 per capsule (PRO 160/120) was investigated in elderly, male patients suffering from lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia in a prospective multicenter trial. A total of 257 patients (129 and 128, respectively) were randomized to treatment with PRO 160/120 or placebo (127 and 126 were evaluable for efficacy). Following a single-blind placebo run-in phase of 2 weeks, the patients received 2 x 1 capsule/day of the study medication under double-blind conditions over a period of 24 weeks. Double-blind treatment was followed by an open control period of 24 weeks during which all patients were administered PRO 160/120. Outcome measures for treatment efficacy included the assessment of the patients' LUTS by means of the I-PSS self-rating questionnaire and a quality of life index as well as uroflow and sonographic parameters. Using the International Prostate Symptom Score (I-PSS), patients treated with PRO 160/120 exhibited a substantially higher total score reduction after 24 weeks of double-blind treatment than patients of the placebo group (6 points vs 4 points; P=0.003, one tailed) with a tendency in the same direction after 16 weeks. This applied to obstructive as well as to irritative symptoms, and to patients with moderate or severe symptoms at baseline. Patients randomized to placebo showed a marked improvement in LUTS (as measured by the I-PSS) after being switched to PRO 160/120 during the control period (P=0.01, one tailed, in comparison to those who had been treated with PRO 160/120 in the double-blind phase). The tolerability of PRO 160/120 was comparable to the placebo. In conclusion, PRO 160/120 was clearly superior to the placebo for the amelioration of LUTS as measured by the I-PSS. PRO 160/120 is advantageous in obstructive and irritative urinary symptoms and in patients with moderate and severe symptoms. The tolerability of the herbal extract was excellent.
To determine the effects of therapy with Urtica dioica for symptomatic relief of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH).
A 6-month, double-blind, placebo-controlled, randomized, partial crossover, comparative trial of Urtica dioica with placebo in 620 patients was conducted. Patients were evaluated using the International Prostate Symptom Score (IPSS), the maximum urinary flow rate (Qmax), postvoid residual urine volume (PVR), Serum Prostatic- Specific Antigen (PSA), testosterone levels, and prostate size. At the end of 6-month trial, unblinding revealed that patients who initially received the placebo were switched to Urtica dioica. Both groups continued the medication up to 18 months.
558 patients (90%) completed the study (287/305, 91% in the Urtica dioica group, and 271/315, 86% in the placebo group). By intention- to-treat analysis, at the end of 6-month trial, 232 (81%) of 287 patients in the Urtica dioica group reported improved LUTS compared with 43 (16%) of 271 patients in the placebo group (P < 0.001). Both IPSS and Qmax showed greater improvement with drug than with placebo. The IPSS went from 19.8 down to 11.8 with Urtica dioica and from 19.2 to 17.7 with placebo (P = 0.002). Peak flow rates improved by 3.4 mL/s for placebo recipients and by 8.2 mL/s for treated patients (P < 0.05). In Urtica dioica group, PVR decreased from an initial value of 73 to 36 mL (P < 0.05). No appreciable change was seen in the placebo group. Serum PSA and testosterone levels were unchanged in both groups. A modest decrease in prostate size as measured by transrectal ultrasonography (TRUS) was seen in Urtica dioica group (from 40.1 cc initially to 36.3 cc; P < 0.001). There was no change in the prostate volume at the end of study with placebo. At 18-month follow-up, only patients who continued therapy, had a favorable treatment variables value. No side effects were identified in either group.
In the present study, Urtica dioica have beneficial effects in the treatment of symptomatic BPH. Further clinical trials should be conducted to confirm these results before concluding that Urtica dioica is effective.
A crude polysaccharide fraction of Urtica fissa roots and stems (UFP) was obtained by water extraction and ultrafiltration, and its effect on castrated rat prostate hyperplasia induced by testosterone propionate was evaluated by the volume index, wet and dry weight index and histopathological tests. Results showed that the crude polysaccharide fraction significantly inhibited prostatic hyperplasia in animal models at doses of 62.5, 125, 250 mg/kg body wt. (administered orally). Treatment with UFP at 62.5 mg/kg body wt. decreased the volume index by 32%, the wet weight index by 17% and the dry weight index by 23%, respectively. In the high-dose group (UFP at 250 mg/kg body wt.), the indexes of volume, wet weight and dry weight decreased further by 37%, 25% and 33%, respectively. Histopathological examination showed that proliferation of prostatic epithelial cells and fibrotic tissues were significantly inhibited.
New perspectives in acute toxicity testing of chemicals Urtica dioica for treatment of benign prostatic hyperplasia: a prospective, randomized, double-blind, placebo-controlled, crossover study
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- Kayser
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Stinging nettle root extract (Bazoton-uno) in long term treatment of benign prostatic syndrome (BPS)
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Serenoa repens (13artram)
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Effect of scopoletin on PC3 cell proliferation and apoptosis
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Stinging nettle root extract (Bazoton-uno) in long term treatment of benign prostatic syndrome (BPS). Results of a randomized, double-blind, placebocontrolled mulicenter study after 12 months
- Schneider